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  • Population dynamics and antigenic drift of Bordetella pertussis following whole cell vaccine replacement, Barcelona, Spain, 1986-2015.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Alba Mir-Cros,Albert Moreno-Mingorance,M Teresa Martín-Gómez,Gema Codina,Thais Cornejo-Sánchez,Mireia Rajadell,Diego Van Esso,Carlos Rodrigo,Magda Campins,Mireia Jané,Tomàs Pumarola,Anna Fàbrega,Juan José González-López

    Among the factors associated with the resurgence of whooping cough, special emphasis has been given to pathogen adaptation after the introduction of the acellular vaccine (ACV). To assess the impact of the vaccine transition strategy from whole-cell vaccine (WCV) to ACV on population dynamics of Bordetella pertussis in Barcelona (Spain), we studied 339 isolates collected from 1986 to 2015 by PFGE and multi-locus variable-number tandem repeat analysis (MLVA). Additionally, allelic variants for the pertussis toxin and its promoter, pertactin, type 3 fimbriae and fimbrial serotyping were assessed to determine its antigenic drift. A shift was observed in the B. pertussis population as well as in its antigenic profile concurrently with the introduction of ACV in Barcelona. Four out of the five most prevalent PFGE profiles were replaced by new profiles following the ACV introduction. MLVA type 27 was the dominant genotype, and its frequency increased from 25% to 79.3% after WCV replacement. Antigen typing demonstrated the emergence of prn2, ptxP3, fim3-2 and a shift from the fimbriae 3 to the fimbriae 2 serotypes after the ACV introduction. Our findings support the presence of population and antigenic dynamic changes in B. pertussis likely driven by the introduction of ACV.

    更新日期:2019-11-01
  • Neutralization sites of human papillomavirus-6 relate to virus attachment and entry phase in viral infection.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Xinlin Liu,Jie Chen,Zhiping Wang,Daning Wang,Maozhou He,Ciying Qian,Shuo Song,Xin Chi,Zhibo Kong,Qingbing Zheng,Yingbin Wang,Hai Yu,Qinjian Zhao,Jun Zhang,Shaowei Li,Ying Gu,Ningshao Xia

    Human papillomavirus type 6 (HPV6) is the major etiologic agent of genital warts and recurrent respiratory papillomatosis. Although the commercial HPV vaccines cover HPV6, the neutralization sites and mode for HPV6 are poorly understood. Here, we identify the HPV6 neutralization sites and discriminate the inhibition of virus attachment and entry by three potent neutralizing antibodies (nAbs), 5D3, 17D5, and 15F7. Mutagenesis assays showed that these nAbs predominantly target surface loops BC, DE, and FG of HPV6 L1. Cryo-EM structures of the HPV6 pseudovirus (PsV) and its immune complexes revealed three distinct binding modalities - full-occupation-bound to capsid, top-center-bound-, and top-rim-bound to pentamers - and illustrated a structural atlas for three classes of antibody-bound footprints that are located at center-distal ring, center, and center-proximal ring of pentamer surface for 5D3, 17D5, and 15F7, respectively. Two modes of neutralization were identified: mAb 5D3 and 17D5 block HPV PsV from attaching to the extracellular matrix (ECM) and the cell surface, whereas 15F7 allows PsV attachment but prohibits PsV from entering the cell. These findings highlight three neutralization sites of HPV6 L1 and outline two antibody-mediated neutralization mechanisms against HPV6, which will be relevant for HPV virology and antiviral inhibitor design. HighlightsMajor neutralization sites of HPV6 were mapped on the pseudovirus cryo-EM structuremAb 15F7 binds HPV6 capsid with a novel top-rim binding modality and confers a post-attachment neutralizationmAb 17D5 binds capsid in top-centre manner but unexpectedly prevents virus from attachment to cell surface.

    更新日期:2019-11-01
  • Identification of a novel RhlI/R-PrrH-LasI/Phzc/PhzD signalling cascade and its implication in P. aeruginosa virulence.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-14
    Yang Lu,Honglin Li,Jieying Pu,Qian Xiao,Chanjing Zhao,Yimei Cai,Yuyang Liu,Lina Wang,Youqiang Li,Bin Huang,Jianming Zeng,Cha Chen

    Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in P. aeruginosa, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the prrH locus sRNA influences P. aeruginosa virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of P. aeruginosa in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the rhl QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the rhl system, on the promoter region of prrH. Further β-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to P. aeruginosa pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in P. aeruginosa and provide new insight into PrrH's function.

    更新日期:2019-11-01
  • Dengue haemorrhagic fever: a job done via exosomes?
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Ritu Mishra,Sneh Lata,Amjad Ali,Akhil C Banerjea

    Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity. Earlier studies have established the fact that dengue virus (DENV) infection causes haemorrhagic fever and shock syndrome, but it is not directly responsible for exhibiting these clinical symptoms. It is noteworthy that clinically, vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines. The onset of hyperpermeability in severe cases of dengue disease takes place around the time of defervescence and after clearance of viraemia. Extracellular vesicles are known to carry biological information (mRNA, miRNA, transcription factors) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals. In dengue virus infection, the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines. Here, we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special focus on the role of secreted extracellular vesicles.

    更新日期:2019-11-01
  • Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Jordi Rodon,Nisreen M A Okba,Nigeer Te,Brenda van Dieren,Berend-Jan Bosch,Albert Bensaid,Joaquim Segalés,Bart L Haagmans,Júlia Vergara-Alert

    The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks pose a worldwide public health threat. Blocking MERS-CoV zoonotic transmission from dromedary camels, the animal reservoir, could potentially reduce the number of primary human cases. Here we report MERS-CoV transmission from experimentally infected llamas to naïve animals. Directly inoculated llamas shed virus for at least 6 days and could infect all in-contact naïve animals 4-5 days after exposure. With the aim to block virus transmission, we examined the efficacy of a recombinant spike S1-protein vaccine. In contrast to naïve animals, in-contact vaccinated llamas did not shed infectious virus upon exposure to directly inoculated llamas, consistent with the induction of strong virus neutralizing antibody responses. Our data provide further evidence that vaccination of the reservoir host may impede MERS-CoV zoonotic transmission to humans.

    更新日期:2019-11-01
  • Potential of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) to transmit yellow fever virus in urban areas in Central Africa.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Basile Kamgang,Marie Vazeille,Aurélie P Yougang,Armel N Tedjou,Theodel A Wilson-Bahun,Laurence Mousson,Charles S Wondji,Anna-Bella Failloux

    Yellow Fever (YF) remains a major public health issue in Sub-Saharan Africa and South America, despite the availability of an effective vaccine. In Africa, most YF outbreaks are reported in West Africa. However, urban outbreaks occurred in 2016 in both Angola and the Democratic Republic of Congo (DRC), and imported cases were reported in Chinese workers coming back from Africa. In Central Africa, Cameroon and the Republic of Congo host a high proportion of non-vaccinated populations increasing the risk of urban outbreaks. The main vector is Aedes aegypti and possibly, Aedes albopictus, both being anthropophilic and domestic mosquitoes. Here, we provide evidence that both Ae. aegypti and Ae. albopictus in Cameroon and the Republic of Congo are able to transmit Yellow fever virus (YFV) with higher rates of infection, dissemination, and transmission for Ae. aegypti. We conclude that the potential of both Aedes species to transmit YFV could increase the risk of urban YF transmission and urge public health authorities to intensify their efforts to control domestic vectors, and extend vaccine coverage to prevent major YFV outbreak.

    更新日期:2019-11-01
  • Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Yang Yang,Ming Xia,Leyi Wang,Sahaana Arumugam,Yajing Wang,Xianjin Ou,Chenlong Wang,Xi Jiang,Ming Tan,Yutao Chen,Xuemei Li

    Diverse noroviruses infect humans and animals via the recognition of host-specific glycan ligands. Genogroup II (GII) noroviruses consist of human noroviruses (huNoVs) that generally bind histo-blood group antigens (HBGAs) as host factors and three porcine norovirus (porNoV) genotypes (GII.11/18/19) that form a genetic lineage lacking HBGA-binding ability. Thus, these GII porNoVs provide an excellent model to study norovirus evolution with host ligand specificity changes. Here we solved the crystal structures of a native GII.11 porNoV P protein and a closely-related GII.3 huNoV P protein complexed with an HBGA, focusing on the HBGA-binding sites (HBSs) compared with the previously known ones to understand the structural basis of the host ligand specificity change. We found that the GII.3 huNoV binds HBGAs via a conventional GII HBS that uses an arginine instead of the conserved aromatic residue for the required Van der Waals interaction, while the GII.11 porNoV HBS loses its HBGA-binding function because of two mutations (Q355/V451). A mutant that reversed the two mutated residues back to the conventional A355/Y451 restored the HBGA-binding function of the GII.11 porNoV P protein, which validated our observations. Similar mutations are also found in GII.19 porNoVs and a GII.19 P protein mutant with double reverse mutations restored the HBS function. This is the first reconstruction of a functional HBS based on one with new host specificity back to its parental one. These data shed light on the molecular basis of structural adaptation of the GII porNoVs to the pig hosts through mutations at their HBSs.

    更新日期:2019-11-01
  • Mechanisms underlying the virulence regulation of new Vibrio alginolyticus ncRNA Vvrr1 with a comparative proteomic analysis.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Yanfei Zuo,Lingmin Zhao,Xiaojin Xu,Jiaonan Zhang,Jiaolin Zhang,Qingpi Yan,Lixing Huang

    The incidence of Vibrio alginolyticus infections has increased in recent years due to the influence of climate change and rising sea temperature. Vibrio virulence regulatory RNA 1 (Vvrr1) is a newly found noncoding RNA (ncRNA) predicted to be closely related to the adhesion ability of V. alginolyticus based on the previous RNA-seq. In this study, the target genes of Vvrr1 were fully screened and verified by constructing Vvrr1-overexpressing strains and using the proteome sequencing technology. Pyruvate kinase I (pykF) gene was predicted to be a chief target gene of Vvrr1 involved in virulence regulation. The adhesion ability, biofilm formation and virulence were significantly reduced in the Vvrr1-overexpressing and the pykF-silenced strain compared with the wild strains. Similar to the overexpression of Vvrr1, the silencing of pykF also reduced the expression level of virulence genes, such as ndk, eno, sdhB, glpF, and cysH. Meanwhile, by constructing the "pykF-GFP" fusion expression plasmid and using the GFP reporter gene analysis in Escherichia coli, the fluorescence intensity of the strain containing Vvrr1 whole ncRNA sequence vector was found to be significantly weakened. These indicated that Vvrr1 participated in the virulence regulation mechanism of V. alginolyticus by interacting with the virulence gene pykF.

    更新日期:2019-11-01
  • Novel FKS1 and FKS2 modifications in a high-level echinocandin resistant clinical isolate of Candida glabrata.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-13
    Xin Hou,Kelley R Healey,Erika Shor,Milena Kordalewska,Cristina Jiménez Ortigosa,Padmaja Paderu,Meng Xiao,He Wang,Ying Zhao,Li-Yan Lin,Yan-Hai Zhang,Yong-Zhe Li,Ying-Chun Xu,David S Perlin,Yanan Zhao

    Echinocandin resistance in Candida glabrata poses a serious clinical challenge. The underlying resistance mechanism of a pan-echinocandin-resistant C. glabrata isolate (strain L74) was investigated in this study. FKS mutants carrying specific mutations found in L74 were reconstructed by the Alt-R CRISPR-Cas9 system (Fks1 WT/Fks2-E655K, strain CRISPR 31) and site-directed mutagenesis (strain fks1Δ/Fks2-E655K). Sequence analysis of strain L74 revealed a premature stop codon W508stop in FKS1 and an E655K mutation preceding the hotspot 1 region in FKS2. Introduction of the Fks2-E655K mutation in ATCC 2001 (strain CRISPR 31) conferred a modest reduction in susceptibility. However, the same FKS2 mutation in the fks1Δ background (strain fks1Δ/Fks2-E655K) resulted in high levels of resistance to echinocandins. Glucan synthase isolated from L74 was dramatically less sensitive to micafungin (MCF) relative to ATCC 2001. Both FKS1/FKS2 transcript ratios and Fks1/Fks2 protein ratios were significantly lower in L74 and fks1Δ/Fks2-E655K compared to ATCC 2001 and CRISPR 31 (P <0.05). Mice challenged with CRISPR 31 and fks1Δ/Fks2-E655K mutants failed to respond to MCF. In conclusion, the high-level of echinocandin resistance in the clinical isolate of C. glabrata L74 was concluded to result from the combination of null function of Fks1 and the point mutation E655K in Fks2.

    更新日期:2019-11-01
  • First case of laboratory-confirmed severe fever with thrombocytopenia syndrome disease revealed the risk of SFTSV infection in Xinjiang, China.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-28
    Liying Zhu,Feifei Yin,Abulimiti Moming,Jingyuan Zhang,Bo Wang,Lijuan Gao,Jianwen Ruan,Qiaoli Wu,Na Wu,Hualin Wang,Fei Deng,Gang Lu,Shu Shen

    The Xinjiang Uygur Autonomous Region locating in Northwest of China was not considered the epidemic area of severe fever with thrombocytopenia syndrome (SFTS). Here we report the first laboratory-confirmed SFTS case that a female patient had tick bite in Xinjiang and illness onset after returning to Hainan Province. Laboratory tests identified SFTS virus (SFTSV) infection, and the virus was isolated from the patient's serum sample. Furthermore, SFTSV prevalence among tick groups was identified, and IgM response to SFTSV from febrile patients was identified. The findings suggested that there have been risks of SFTSV infection due to exposure to ticks in Xinjiang.

    更新日期:2019-11-01
  • The African strain of Zika virus causes more severe in utero infection than Asian strain in a porcine fetal transmission model.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-26
    Daniel Udenze,Ivan Trus,Nathalie Berube,Volker Gerdts,Uladzimir Karniychuk

    Studies in mice showed that African Zika virus (ZIKV) strains cause more damage in embryos. These studies, however, were limited to the mouse-adapted African MR766 strain or infection at early gestation. Here, we compared infection of Asian and African strains in the fetal pig model at midgestation. Both strains caused fetal infection. ZIKV was detected in placenta, amniotic membrane, amniotic fluid, fetal blood, and brain. The African strain produced more vigorous in utero infection as represented by more efficient virus transmission between siblings, and higher viral loads in fetal organs and membranes. Infection with both strains was associated with reduced fetal brain weight and increased number of placental CD163-positive cells, as well as elevated in utero interferon alpha and cortisol levels. This is the first large animal model study which demonstrated that African strain of ZIKV, with no passage history in experimental animals, can cause persistent infection in fetuses and fetal membranes at midgestation. Our studies also suggest that similar to Asian strains, ZIKV of African lineage might cause silent pathology which is difficult to identify in deceptively healthy fetuses. The findings emphasize the need for further studies to highlight the impact of ZIKV heterogeneity on infection outcomes during pregnancy.

    更新日期:2019-11-01
  • Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-26
    Nancy M Cladel,Pengfei Jiang,Jingwei J Li,Xuwen Peng,Timothy K Cooper,Vladimir Majerciak,Karla K Balogh,Thomas J Meyer,Sarah A Brendle,Lynn R Budgeon,Debra A Shearer,Regina Munden,Maggie Cam,Raghavan Vallur,Neil D Christensen,Zhi-Ming Zheng,Jiafen Hu

    Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

    更新日期:2019-11-01
  • Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-25
    Xi Yang,Xiang Wang,Yufeng Song,Ping Zhou,Dapeng Li,Chao Zhang,Xia Jin,Zhong Huang,Dongming Zhou

    In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.

    更新日期:2019-11-01
  • Hepatitis E-related adverse pregnancy outcomes and their prevention by hepatitis E vaccine in a rabbit model.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-25
    Manyu Li,Shuangshuang Li,Qiyu He,Zhaochao Liang,Lin Wang,Qianhui Wang,Ling Wang

    Hepatitis E virus (HEV) can lead to high mortality during pregnancy. This study was to investigate the adverse pregnancy outcomes caused by different HEV genotypes and their prevention by HEV 239 vaccine in rabbits. Forty-two female rabbits were randomly and equally divided into 7 groups (A-G). HEV 239 vaccine and a placebo were administered to groups E (10 μg×2), F (5 μg×2) and G (1 mL of PBS×2) before copulation. After pregnancy, 1 mL of 1.5×106 copies/mL rabbit HEV3 was inoculated to groups A, E, F and G, swine HEV4/human HEV3 to groups B/C, and group D was a negative control. Anti-HEV antibody, HEV RNA, and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels were monitored. Pregnant rabbits infected by HEV manifested HEV infection symptoms including fecal virus shedding, ALT/AST elevation, and histopathological changes, and adverse pregnancy outcomes. Immunized pregnant rabbits in groups E and F showed no HEV infection symptoms and adverse outcomes. The newborn rabbits delivered by pregnant rabbits with/without immunization showed without/with HEV infection symptoms. This study demonstrated that multiple genotypes of HEV infection can cause adverse outcomes and HEV 239 vaccine can prevent HEV-related adverse outcomes in pregnant rabbits.

    更新日期:2019-11-01
  • Intra-host emergence of an enterovirus A71 variant with enhanced PSGL1 usage and neurovirulence.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-25
    Liang Sun,Aloys Tijsma,Carmen Mirabelli,Jim Baggen,Maryam Wahedi,David Franco,Armando De Palma,Pieter Leyssen,Erik Verbeken,Frank J M van Kuppeveld,Johan Neyts,Hendrik Jan Thibaut

    Enterovirus A71 (EV-A71) is one of the main causative agents of hand-foot-and-mouth disease and is occasionally associated with severe neurological complications. EV-A71 pathophysiology is poorly understood due to the lack of small animal models that robustly support viral replication in relevant organs/tissues. Here, we show that adult severe combined immune-deficient (SCID) mice can serve as an EV-A71 infection model to study neurotropic determinants and viral tropism. Mice inoculated intraperitoneally with an EV-A71 clinical isolate had an initial infection of the lung compartment, followed by neuroinvasion and infection of (motor)neurons, resulting in slowly progressing paralysis of the limbs. We identified a substitution (V135I) in the capsid protein VP2 as a key requirement for neurotropism. This substitution was also present in a mouse-adapted variant, obtained by passaging the clinical isolate in the brain of one-day-old mice, and induced exclusive neuropathology and rapid paralysis, confirming its role in neurotropism. Finally, we showed that this residue enhances the capacity of EV-A71 to use mouse PSGL1 for viral entry. Our data reveal that EV-A71 initially disseminates to the lung and identify viral and host determinants that define the neurotropic character of EV-A71, pointing to a hitherto understudied role of PSGL1 in EV-A71 tropism and neuropathology.

    更新日期:2019-11-01
  • Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-25
    Unai Pérez-Sautu,Michael Ross Wiley,María Iglesias-Caballero,Francisco Pozo,Karla Prieto,Joseph Alex Chitty,María Luz García-García,Cristina Calvo,Inmaculada Casas,Gustavo Palacios

    Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT-PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.

    更新日期:2019-11-01
  • Tularemia as a waterborne disease: a review.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-10
    Aurélie Hennebique,Sandrine Boisset,Max Maurin

    Francisella tularensis is a Gram-negative, intracellular bacterium causing the zoonosis tularemia. This highly infectious microorganism is considered a potential biological threat agent. Humans are usually infected through direct contact with the animal reservoir and tick bites. However, tularemia cases also occur after contact with a contaminated hydro-telluric environment. Water-borne tularemia outbreaks and sporadic cases have occurred worldwide in the last decades, with specific clinical and epidemiological traits. These infections represent a major public health and military challenge. Human contaminations have occurred through consumption or use of F. tularensis-contaminated water, and various aquatic activities such as swimming, canyoning and fishing. In addition, in Sweden and Finland, mosquitoes are primary vectors of tularemia due to infection of mosquito larvae in contaminated aquatic environments. The mechanisms of F. tularensis survival in water may include the formation of biofilms, interactions with free-living amoebae, and the transition to a 'viable but nonculturable' state, but the relative contribution of these possible mechanisms remains unknown. Many new aquatic species of Francisella have been characterized in recent years. F. tularensis likely shares with these species an ability of long-term survival in the aquatic environment, which has to be considered in terms of tularemia surveillance and control.

    更新日期:2019-11-01
  • Comprehensive subspecies identification of 175 nontuberculous mycobacteria species based on 7547 genomic profiles.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-10
    Yuki Matsumoto,Takeshi Kinjo,Daisuke Motooka,Daijiro Nabeya,Nicolas Jung,Kohei Uechi,Toshihiro Horii,Tetsuya Iida,Jiro Fujita,Shota Nakamura

    The prevalence of nontuberculous mycobacteria (NTM) pulmonary diseases has been increasing worldwide. NTM consist of approximately 200 species and distinguishing between them at the subspecies level is critical to treatment. In this study, we sequenced 63 NTM genomes, 27 of which were newly determined, by hybrid assembly using sequencers from Illumina and Oxford Nanopore Technologies (ONT). This analysis expanded the available genomic data to 175 NTM species and redefined their subgenus classification. We also developed a novel multi-locus sequence typing (MLST) database based on 184 genes from 7547 assemblies and an identification software, mlstverse, which can also be used for detecting other bacteria given a suitable MLST database. This method showed the highest sensitivity and specificity amongst conventional methods and demonstrated the capacity for rapid detection of NTM, 10 min of sequencing of the ONT MinION being sufficient. Application of this methodology could improve disease epidemiology and increase the cure rates of NTM diseases.

    更新日期:2019-11-01
  • Characterization of swine-origin H1N1 canine influenza viruses.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-10
    Guojun Wang,Luiz Gustavo Dos Anjos Borges,Daniel Stadlbauer,Irene Ramos,Maria C Bermúdez González,Jianqiao He,Yangbao Ding,Zuzhang Wei,Kang Ouyang,Weijian Huang,Viviana Simon,Ana Fernandez-Sesma,Florian Krammer,Martha I Nelson,Ying Chen,Adolfo García-Sastre

    Host switch events of influenza A viruses (IAVs) continuously pose a zoonotic threat to humans. In 2013, swine-origin H1N1 IAVs emerged in dogs soon after they were detected in swine in the Guangxi province of China. This host switch was followed by multiple reassortment events between these H1N1 and previously circulating H3N2 canine IAVs (IAVs-C) in dogs. To evaluate the phenotype of these newly identified viruses, we characterized three swine-origin H1N1 IAVs-C and one reassortant H1N1 IAV-C. We found that H1N1 IAVs-C predominantly bound to human-type receptors, efficiently transmitted via direct contact in guinea pigs and replicated in human lung cells. Moreover, the swine-origin H1N1 IAVs-C were lethal in mice and were transmissible by respiratory droplets in guinea pigs. Importantly, sporadic human infections with these viruses have been detected, and preexisting immunity in humans might not be sufficient to prevent infections with these new viruses. Our results show the potential of H1N1 IAVs-C to infect and transmit in humans, suggesting that these viruses should be closely monitored in the future.

    更新日期:2019-11-01
  • The dynamics and interactions of respiratory pathogen carriage among French pilgrims during the 2018 Hajj.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Van-Thuan Hoang,Thi-Loi Dao,Tran Duc Anh Ly,Khadidja Belhouchat,Kamel Larbi Chaht,Jean Gaudart,Bakridine Mmadi Mrenda,Tassadit Drali,Saber Yezli,Badriah Alotaibi,Pierre-Edouard Fournier,Didier Raoult,Philippe Parola,Vincent Pommier de Santi,Philippe Gautret

    We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria.

    更新日期:2019-11-01
  • Are adenoviruses zoonotic? A systematic review of the evidence.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Laura K Borkenhagen,Jane K Fieldhouse,Donald Seto,Gregory C Gray

    Adenoviruses (AdVs) are major contributors to clinical illnesses. Novel human and animal AdVs continue to be identified and characterized. Comparative analyses using bioinformatic methods and Omics-based technologies allow insights into how these human pathogens have emerged and their potential for host cross-species transmission. Systematic review of literature published across ProQuest, Pubmed, and Web of Science databases for evidence of adenoviral zoonotic potential identified 589 citations. After removing duplicates, 327 citations were screened for relevance; of which, 74 articles received full-text reviews. Among these, 24 were included here, of which 16 demonstrated evidence of zoonotic transmission of AdVs. These documented instances of AdV crossing host species barriers between humans and non-human primate, bat, feline, swine, canine, ovine, and caprine. Eight studies sought to but did not find evidence of zoonosis. The findings demonstrate substantial evidence suggesting AdVs have previously and will continue crossing host species barriers. These have human health consequences both in terms of novel pathogen emergence and epidemic outbreaks, and of appropriate and safe use of non-human adenoviruses for therapeutics. As routine human clinical diagnostics may miss a novel cross-species adenovirus infection in humans, next generation sequencing or panspecies molecular diagnostics may be necessary to detect such incursions.

    更新日期:2019-11-01
  • Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases: a molecular and evolutionary study.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Jung Hun Lee,Masayuki Takahashi,Jeong Ho Jeon,Lin-Woo Kang,Mineaki Seki,Kwang Seung Park,Myoung-Ki Hong,Yoon Sik Park,Tae Yeong Kim,Asad Mustafa Karim,Jung-Hyun Lee,Masayuki Nashimoto,Sang Hee Lee

    Resistance to β-lactams is one of the most serious problems associated with Gram-negative infections. β-Lactamases are able to hydrolyze β-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-β-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.

    更新日期:2019-11-01
  • Antigenic variations of recent street rabies virus.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-05
    Wenbo Wang,Jian Ma,Jianhui Nie,Jia Li,Shouchun Cao,Lan Wang,Chuanfei Yu,Weijin Huang,Yuhua Li,Yongxin Yu,Mifang Liang,Brett Zirkle,Xiaojiang S Chen,Xuguang Li,Wei Kong,Youchun Wang

    The genetic and/or antigenic differences between street rabies virus (RABV) and vaccine strains could potentially affect effectiveness of rabies vaccines. As such, it is important to continue monitoring the glycoprotein (G) of the street isolates. All RABVG sequences in public database were retrieved and analysed. Using a pseudovirus system, we investigated 99 naturally occurring mutants for their reactivities to well-characterized neutralizing monoclonal antibodies (mAbs) and vaccine-induced antisera. A divergence in G sequences was found between vaccine strains and recent street isolates, with mutants demonstrating resistance to neutralizing mAbs and vaccine-induced antibodies. Moreover, antigenic variants were observed in a wide range of animal hosts and geographic locations, with most of them emerging since 2010. As the number of antigenic variants has increased in recent years, close monitoring on street isolates should be strengthened.

    更新日期:2019-11-01
  • Visualization of chikungunya virus infection in vitro and in vivo.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-05
    Hong-Lei Zhang,Hao-Long Dong,Ya-Nan Zhang,Lin-Lin Xu,Cheng-Lin Deng,Xiao-Feng Li,Xiao-Dan Li,Han-Qing Ye,Zhi-Ming Yuan,Cheng-Feng Qin,Bo Zhang

    Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR-/- A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.

    更新日期:2019-11-01
  • Zika virus threshold determines transmission by European Aedes albopictus mosquitoes.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : null
    Marie Vazeille,Yoann Madec,Laurence Mousson,Rachel Bellone,Hélène Barré-Cardi,Carla Alexandra Sousa,Davy Jiolle,André Yébakima,Xavier de Lamballerie,Anna-Bella Failloux

    Since its emergence in Yap Island in 2007, Zika virus (ZIKV) has affected all continents except Europe. Despite the hundreds of cases imported to European countries from ZIKV-infested regions, no local cases have been reported in localities where the ZIKV-competent mosquito Aedes albopictus is well established. Here we analysed the vector competence of European Aedes (aegypti and albopictus) mosquitoes to different genotypes of ZIKV. We demonstrate that Ae. albopictus from France was less susceptible to the Asian ZIKV than to the African ZIKV. Critically we show that effective crossing of anatomical barriers (midgut and salivary glands) after an infectious blood meal depends on a viral load threshold to trigger: (i) viral dissemination from the midgut to infect mosquito internal organs and (ii) viral transmission from the saliva to infect a vertebrate host. A viral load in body ≥4800 viral copies triggered dissemination and ≥12,000 viral copies set out transmission. Only 27.3% and 18.2% of Ae. albopictus Montpellier mosquitoes meet respectively these two criteria. Collectively, these compelling results stress the poor ability of Ae. albopictus to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.

    更新日期:2019-11-01
  • Simultaneous outbreaks of respiratory disease in wild chimpanzees caused by distinct viruses of human origin.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-03-15
    Jacob D Negrey,Rachna B Reddy,Erik J Scully,Sarah Phillips-Garcia,Leah A Owens,Kevin E Langergraber,John C Mitani,Melissa Emery Thompson,Richard W Wrangham,Martin N Muller,Emily Otali,Zarin Machanda,David Hyeroba,Kristine A Grindle,Tressa E Pappas,Ann C Palmenberg,James E Gern,Tony L Goldberg

    Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. The viruses were absent before the outbreaks, but each was present in ill chimpanzees from one community during the outbreak period. Clinical signs and gross pathologic changes in affected chimpanzees closely mirrored symptoms and pathology commonly observed in humans for each virus. Epidemiologic modelling showed that MPV and HRV3 were similarly transmissible (R0 of 1.27 and 1.48, respectively), but MPV caused 12.2% mortality mainly in infants and older chimpanzees, whereas HRV3 caused no direct mortality. These results are consistent with the higher virulence of MPV than HRV3 in humans, although both MPV and HRV3 cause a significant global disease burden. Both viruses clustered phylogenetically within groups of known human variants, with MPV closely related to a lethal 2009 variant from mountain gorillas (Gorilla beringei beringei), suggesting two independent and simultaneous reverse zoonotic origins, either directly from humans or via intermediary hosts. These findings expand our knowledge of human origin viruses threatening wild chimpanzees and suggest that such viruses might be differentiated by their comparative epidemiological dynamics and pathogenicity in wild apes. Our results also caution against assuming common causation in coincident outbreaks.

    更新日期:2019-11-01
  • Keeping all secondary structures of the non-coding region in the circular genome of human bocavirus 2 is important for DNA replication and virus assembly, as revealed by three hetero-recombinant genomic clones.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-11-02
    Linqing Zhao,Tao Wang,Yuan Qian,Jingdong Song,Runan Zhu,Liying Liu,Liping Jia,Huijin Dong

    The episomal structures of all human bocavirus (HBoV) genotypes have been deciphered, including the circular genome of HBoV2 (HBoV2-C1). To discern the role of the circular HBoV2 genome, three distinct linearized HBoV2-C1 genomes were cloned into pBlueScript SKII(+) to obtain pBlueScript HBoV2 5043-5042 (retaining all secondary structures), pBlueScript-HBoV2 5075-5074 (retaining hairpin number 2 and the 5' terminal structure), and pBlueScript-HBoV2 5220-5219 (retaining only the 5' terminal structure at the 5' -genome end). The recombinant plasmids were separately transfected HEK293 cells, revealing that more HBoV2 DNA had accumulated in the pBlueScript HBoV2 5043-5042-transfected HEK293 cells at 72 h post-transfection, as determined by real-time PCR. However, more mRNA was transcribed by pBlueScript-HBoV2 5075-5074 than by the other constructs, as determined by dot-blot hybridization and RNAscope. No significant differences in NS1-70 protein expression were observed among the three HBoV2 genomic clones. However, electron microscopy showed that HBoV2 virus particles were only present in the pBlueScript HBoV2 5043-5042-transfected HEK293 cells. By using three hetero-recombinant HBoV2 genomic clones in HEK293 transfected cells, only the genome with intact secondary structures produced virus particles, suggesting that retaining these structures in a circular genome is important for HBoV2 DNA replication and virus assembly.

    更新日期:2019-11-01
  • Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-10
    Pauline Ferraris,Marielle Cochet,Rodolphe Hamel,Ivan Gladwyn-Ng,Christian Alfano,Fodé Diop,Déborah Garcia,Loïc Talignani,Claudia N Montero-Menei,Antoine Nougairède,Hans Yssel,Laurent Nguyen,Muriel Coulpier,Dorothée Missé

    Zika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease with particular neurological complications, including Guillain-Barré Syndrome and congenital microcephaly. Although ZIKV has been shown to directly infect human neural progenitor cells (hNPCs), thereby decreasing their viability and growth, it is as yet unknown which of the cellular pathways involved in the disruption of neurogenesis are affected following ZIKV infection. By comparing the effect of two ZIKV strains in vitro on hNPCs, the differentiation process of the latter cells was found to lead to a decreased susceptibility to infection and cell death induced by each of the ZIKV strains, which was associated with an earlier and stronger antiviral innate immune response in infected, differentiated hNPCs, as compared to undifferentiated cells. Moreover, ZIKV modulated, both in hNPCs and in vivo in fetal brain in an experimental mouse model, the expression of the Notch pathway which is involved in cellular proliferation, apoptosis and differentiation during neurogenesis. These results show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury.

    更新日期:2019-11-01
  • Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-04
    Wenfei Zhu,Zhaomin Feng,Yongkun Chen,Lei Yang,Jia Liu,Xiyan Li,Suli Liu,Lijuan Zhou,Hejiang Wei,Rongbao Gao,Dayan Wang,Yuelong Shu

    It has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.

    更新日期:2019-11-01
  • Klebsiella variicola: an emerging pathogen in humans.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-02
    Nadia Rodríguez-Medina,Humberto Barrios-Camacho,Josefina Duran-Bedolla,Ulises Garza-Ramos

    The Klebsiella pneumoniae complex comprises seven K. pneumoniae-related species, including K. variicola. K. variicola is a versatile bacterium capable of colonizing different hosts such as plants, humans, insects and animals. Currently, K. variicola is gaining recognition as a cause of several human infections; nevertheless, its virulence profile is not fully characterized. The clinical significance of K. variicola infection is hidden by imprecise detection methods that underestimate its real prevalence; however, several methods have been developed to correctly identify this species. Recent studies of carbapenemase-producing and colistin-resistant strains demonstrate a potential reservoir of multidrug-resistant genes. This finding presents an imminent scenario for spreading antimicrobial resistant genes among close relatives and, more concerningly, in clinical and environmental settings. Since K. variicola was identified as a novel bacterial species, different research groups have contributed findings elucidating this pathogen; however, important details about its epidemiology, pathogenesis and ecology are still missing. This review highlights the most significant aspects of K. variicola, discussing its different phenotypes, mechanisms of resistance, and virulence traits, as well as the types of infections associated with this pathogen.

    更新日期:2019-11-01
  • The native European Aedes geniculatus mosquito species can transmit chikungunya virus.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-07-02
    Jorian Prudhomme,Albin Fontaine,Guillaume Lacour,Jean-Charles Gantier,Laure Diancourt,Enkelejda Velo,Silva Bino,Paul Reiter,Aurélien Mercier

    Europe is the world's leading tourism destination and is receiving every year travellers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector Aedes albopictus. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of Aedes geniculatus, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with an European population of Ae. albopictus. We revealed that Ae. geniculatus is highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in Ae. geniculatus was delayed by several days as compared to Ae. albopictus. Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.

    更新日期:2019-11-01
  • Babesia divergens in human in Gansu province, China.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-28
    Jinming Wang,Shangdi Zhang,Jingqiong Yang,Junlong Liu,Dekui Zhang,Youquan Li,Jianxun Luo,Guiquan Guan,Hong Yin

    Human babesiosis is an important tick-borne infectious disease. We investigated human babesiosis in the Gansu province and found that it is prevalent in this area with a prevalence of 1.3%. Results of gene sequencings indicate that 1.3% of patients were positive for Babesia divergens. This initial report of human B. divergens infections in Gansu Province should raise awareness of human babesiosis.

    更新日期:2019-11-01
  • Identification of a novel alphavirus related to the encephalitis complexes circulating in southern Brazil.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-27
    Marcel Kruchelski Tschá,Andreia Akemi Suzukawa,Tiago Gräf,Laercio Dante Stein Piancini,Allan Martins da Silva,Helisson Faoro,Irina Nastassja Riediger,Lia Carolina Medeiros,Pryscilla Fanini Wowk,Camila Zanluca,Claudia Nunes Duarte Dos Santos

    In early 2017, an outbreak caused by an unknown and supposedly viral agent in the Marilena region of southern Brazil was investigated. Since the etiological agent causing the outbreak was not identified from human samples, mosquitoes from this region were collected. Three out of 121 mosquito pools collected from the region tested positive for alphavirus in molecular tests. Next generation sequencing results revealed the presence of a novel alphavirus, tentatively named here as Caainguá virus (CAAV). DNA barcoding analyses indicated that different species of Culex are hosts for CAAV. This new virus was basal to the New World encephalitic alphaviruses in a comprehensive and robust phylogenetic approach using complete genomes. Viral particles were observed in the cytosol and inside of intracellular compartments of cells in mosquito-derived cell cultures. Despite being noninfectious in vertebrate derived cell cultures, primary culturing of CAAV in human mononuclear cells suggests monocytes and lymphocytes as CAAV targets. However, the epidemiological link of CAAV on the human outbreak should be further explored.

    更新日期:2019-11-01
  • Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-27
    Hong-Il Kim,Na-Young Ha,Gwanghun Kim,Chan-Ki Min,Yuri Kim,Nguyen Thi Hai Yen,Myung-Sik Choi,Nam-Hyuk Cho

    Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Despite the wide range of approaches explored during the last seventy years, an effective prophylactic vaccine is not yet available. Here, we developed a novel recombinant antigen derived from conserved regions of 56 kDa type-specific antigen (TSA56), a major outer membrane protein responsible for genetic heterogeneity and antigenicity, and evaluated it as a protective vaccine antigen. Our findings demonstrate that immunization with conserved blocks of TSA56 (cTSA56) not only provides protective immunity against lethal challenges with the homologous genotype, but also confers significantly better protection against heterologous genotypes than TSA56. Adoptive transfer of CD4+ or CD8+ T cells from immunized mice provided significantly enhanced protection against lethal challenge, whereas immune B cells failed to do so, indicating that cellular immunity against the conserved epitopes plays a protective role. Moreover, immunization with a 10-mer peptide mixture, screened from CD8+ T cell epitopes within the conserved region of TSA56, provided enhanced protection against lethal challenge with O. tsutsugamushi. Therefore, this novel recombinant antigen is a promising candidate for scrub typhus vaccine against a wide range of O. tsutsugamushi genotypes.

    更新日期:2019-11-01
  • Vibrio vulnificus RtxA1 cytotoxin targets filamin A to regulate PAK1- and MAPK-dependent cytoskeleton reorganization and cell death.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-27
    Rui Hong Guo,Young Jun Im,Soo Im Shin,Kwangjoon Jeong,Joon Haeng Rhee,Young Ran Kim

    Cytoskeletal rearrangement and acute cytotoxicity occur in Vibrio vulnificus-infected host cells. RtxA1 toxin, a multifunctional autoprocessing repeats-in-toxin (MARTX), is essential for the pathogenesis of V. vulnificus and the programmed necrotic cell death. In this study, HeLa cells expressing RtxA1 amino acids 1491-1971 fused to GFP were observed to be rounded. Through yeast two-hybrid screening and subsequent immunoprecipitation validation assays, we confirmed the specific binding of a RtxA11491-1971 fragment with host-cell filamin A, an actin cross-linking scaffold protein. Downregulation of filamin A expression decreased the cytotoxicity of RtxA1 toward host cells. Furthermore, the phosphorylation of JNK and p38 MAPKs was induced by the RtxA1-filamin A interaction during the toxin-mediated cell death. However, the phosphorylation of these MAPKs was not observed during the RtxA1 intoxication of filamin A-deficient M2 cells. In addition, the depletion of pak1, which appeared to be activated by the RtxA1-filamin A interaction, inhibited RtxA1-induced phosphorylation of JNK and p38, and the cells treated with a pak1 inhibitor exhibited decreased RtxA1-mediated cytoskeletal rearrangement and cytotoxicity. Thus, the binding of filamin A by the RtxA11491-1971 domain appears to be a requisite to pak1-mediated MAPK activation, which contributes to the cytoskeletal reorganization and host cell death.

    更新日期:2019-11-01
  • The scrub typhus in mainland China: spatiotemporal expansion and risk prediction underpinned by complex factors.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-25
    Hongwu Yao,Yixing Wang,Xianmiao Mi,Ye Sun,Kun Liu,Xinlou Li,Xiang Ren,Mengjie Geng,Yang Yang,Liping Wang,Wei Liu,Liqun Fang

    In mainland China, a geographic northward expansion of scrub typhus has been seen, highlighting the need to understand the factors and identify the risk for disease prevention. Incidence data from 1980 to 2013 were used. A Cox proportional hazard model was used to identify drivers for spatial spread, and a boosted regression tree (BRT) model was constructed to predict potential risk areas. Since the 1980s, an invasive expansion from South Natural Foci towards North Natural Foci was clearly identified, with the epidemiological heterogeneity observed between two regions, mainly in spatial distribution, seasonality, and demographic characteristics. Survival analysis disclosed significant factors contributing to the spatial expansion as following: being intersected by freeway (HR = 1.31, 95% CI: 1.11-1.54), coverage percentage of broadleaf forest (HR = 1.10, 95% CI: 1.06-1.15), and monthly average temperature (HR = 1.27, 95% CI: 1.25-1.30). The BRT models showed that precipitation, sunshine hour, temperature, crop field, and relative humidity contributed substantially to the spatial distribution of scrub typhus. A county-scale risk map was created to predict the regions with high probability of the disease. The current study enabled a comprehensive overview of epidemiological characteristics of scrub typhus in mainland China.

    更新日期:2019-11-01
  • Cisplatin protects mice from challenge of Cryptococcus neoformans by targeting the Prp8 intein.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-06-22
    Zhong Li,Bin Fu,Cathleen M Green,Binbin Liu,Jing Zhang,Yuekun Lang,Sudha Chaturvedi,Marlene Belfort,Guojian Liao,Hongmin Li

    The Prp8 intein is one of the most widespread eukaryotic inteins, present in important pathogenic fungi, including Cryptococcus and Aspergillus species. Because the processed Prp8 carries out essential and non-redundant cellular functions, a Prp8 intein inhibitor is a mechanistically novel antifungal agent. In this report, we demonstrated that cisplatin, an FDA-approved cancer drug, significantly arrested growth of Prp8 intein-containing fungi C. neoformans and C. gattii, but only poorly inhibited growth of intein-free Candida species. These results suggest that cisplatin arrests fungal growth through specific inhibition of the Prp8 intein. Cisplatin was also found to significantly inhibit growth of C. neoformans in a mouse model. Our results further showed that cisplatin inhibited Prp8 intein splicing in vitro in a dose-dependent manner by direct binding to the Prp8 intein. Crystal structures of the apo- and cisplatin-bound Prp8 inteins revealed that two degenerate cisplatin molecules bind at the intein active site. Mutation of the splicing-site residues led to loss of cisplatin binding, as well as impairment of intein splicing. Finally, we found that overexpression of the Prp8 intein in cryptococcal species conferred cisplatin resistance. Overall, these results indicate that the Prp8 intein is a novel antifungal target worth further investigation.

    更新日期:2019-11-01
  • Different molecular characteristics and antimicrobial resistance profiles of Clostridium difficile in the Asia-Pacific region.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-31
    Yun Luo,Elaine Cheong,Qiao Bian,Deirdre A Collins,Julian Ye,Jeong Hwan Shin,Wing Cheong Yam,Tohru Takata,Xiaojun Song,Xianjun Wang,Mini Kamboj,Thomas Gottlieb,Jianmin Jiang,Thomas V Riley,Yi-Wei Tang,Dazhi Jin

    Molecular epidemiology of Clostridium difficile infection (CDI) has been extensively studied in North America and Europe; however, limited data on CDI are available in the Asia-Pacific region. A multicentre retrospective study was conducted in this region. C. difficile isolates were subjected to multilocus sequence typing (ST) and antimicrobial susceptibility testing. Totally, 394 isolates were collected from Hangzhou, Hong Kong, China; Busan, South Korea; Fukuoka, Japan; Singapore; Perth, Sydney, Australia; New York, the United States. C. difficile isolates included 337 toxin A-positive/B-positive/binary toxin-negative (A+B+CDT-), 48 A-B+CDT-, and nine A+B+CDT+. Distribution of dominant STs varied geographically with ST17 in Fukuoka (18.6%), Busan (56.0%), ST2 in Sydney (20.4%), Perth (25.8%). The antimicrobial resistance patterns were significantly different among the eight sites (χ2 = 325.64, p < 0.001). Five major clonal complexes correlated with unique antimicrobial resistances. Healthcare-associated (HA) CDI was mainly from older patients with more frequent antimicrobial use and higher A-B+ positive rates. Higher resistance to gatifloxacin, tetracycline, and erythromycin were observed in HA-CDI patients (χ2 = 4.76-7.89, p = 0.005-0.029). In conclusion, multiple C. difficile genotypes with varied antimicrobial resistance patterns have been circulating in the Asia-Pacific region. A-B+ isolates from older patients with prior antimicrobial use were correlated with HA-CDI.

    更新日期:2019-11-01
  • Human infection with a novel reassortant Eurasian-avian lineage swine H1N1 virus in northern China.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-30
    Xiaoyan Li,Liru Guo,Caixia Liu,Yanhui Cheng,Mei Kong,Lei Yang,Zhichao Zhuang,Jia Liu,Ming Zou,Xiaochun Dong,Xu Su,Qing Gu

    Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.

    更新日期:2019-11-01
  • Direct evidence of an extra-intestinal cycle of Toxoplasma gondii in tigers (Panthera tigris) by isolation of viable strains.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-30
    Yurong Yang,Hui Dong,Ruijing Su,Nan Jiang,Tongyi Li,Chunlei Su,Ziguo Yuan,Longxian Zhang

    Toxoplasmosis is one of the most common zoonotic diseases in the world. Felines excrete environmentally resistant Toxoplasma gondii oocysts. However, there is no direct evidence to prove tigers are the intermediate host of T. gondii. Here, we show that, IgG antibodies to T. gondii in 80% (8/10) of captive tigers. Two viable T. gondii strains (ToxoDB genotype #9) were isolated by bioassay in mice using striated muscles of two tigers (Tiger#3 and Tiger#8). Additionally, mice were confirmed as T. gondii-positive by bioassay of feces #89-110, but no viable T. gondii strain was isolated successfully. The fecal samples from tigers may contain T. gondii oocysts. This is the first report of T. gondii isolation from tigers. These results provide direct evidence that an extra-intestinal cycle of T. gondii may develop in tigers.

    更新日期:2019-11-01
  • Identification of multidrug-resistant Neisseria gonorrhoeae isolates with combined resistance to both ceftriaxone and azithromycin, China, 2017-2018.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-30
    Qianqin Yuan,Yamei Li,Leshan Xiu,Chi Zhang,Yaoyang Fu,Chuanhao Jiang,Lingli Tang,Junping Peng

    The growing multidrug-resistant Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. During 2017-2018, we identified a rare multidrug-resistant (ceftriaxone and azithromycin) strain (GC250) and four strains (GC185, GC195, GC196 and GC249) with both resistance to ceftriaxone and decreased susceptibility to azithromycin. All strains belonged to NG-STAR ST1143, including the mosaic penA-60.001, which is closely related to ceftriaxone resistance. The characterization of antimicrobial resistance (AMR) determinants and phylogenetic analysis showed these five strains were closely related to internationally spreading ceftriaxone-resistant N. gonorrhoeae FC428, but with higher azithromycin MIC. Findings here demonstrated that this clone not only initiated clonal expansion in China, but acquired azithromycin resistance.

    更新日期:2019-11-01
  • Serological evidence of MERS-CoV and HKU8-related CoV co-infection in Kenyan camels.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-28
    Wei Zhang,Xiao-Shuang Zheng,Bernard Agwanda,Sheila Ommeh,Kai Zhao,Jacqueline Lichoti,Ning Wang,Jing Chen,Bei Li,Xing-Lou Yang,Shailendra Mani,Kisa-Juma Ngeiywa,Yan Zhu,Ben Hu,Samson Omondi Onyuok,Bing Yan,Danielle E Anderson,Lin-Fa Wang,Peng Zhou,Zheng-Li Shi

    Dromedary camels are important reservoir hosts of various coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) that cause human infections. CoV genomes regularly undergo recombination during infection as observed in bat SARS-related CoVs. Here we report for the first time that only a small proportion of MERS-CoV receptor-binding domain positive (RBD) of spike protein positive camel sera in Kenya were also seropositive to MERS-CoV nucleocapsid (NP). In contrast, many of them contain antibodies against bat HKU8-related (HKU8r)-CoVs. Among 584 camel samples that were positive against MERS-CoV RBD, we found only 0.48 (8.22%) samples were also positive for NP. Furthermore, we found bat HKU8r-CoV NP antibody in 73 (12.5%) of the MERS-CoV RBD positive and NP negative samples, yet found only 3 (0.43%) of the HKU8r-CoV S1 antibody in the same samples. These findings may indicate co-infection with MERS-CoV and a HKU8r-CoV in camels. It may also raise the possibility of the circulation of a recombinant coronavirus virus with the spike of MERS-CoV and the NP of a HKU8r-CoV in Kenya. We failed to find molecular evidence of an HKU8r-CoV or a putative recombinant virus. Our findings should alert other investigators to look for molecular evidence of HKU8r-CoV or recombinants.

    更新日期:2019-11-01
  • Demographic and clinical characteristics of chikungunya patients from six Colombian cities, 2014-2015.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-22
    Juan C Rueda,Ana M Santos,Jose-Ignacio Angarita,Rodrigo B Giraldo,Eugenia-Lucia Saldarriaga,Jesús Giovanny Ballesteros Muñoz,Elías Forero,Hugo Valencia,Francisco Somoza,Daniel Martin-Arsanios,Elias-Josué Quintero,Viviana Reyes-Martinez,Diana Padilla,Francy M Cuervo,Ingris Peláez-Ballestas,Mario H Cardiel,Paula X Pavía,John Londono

    In 2014, the chikungunya virus reached Colombia for the first time, resulting in a nationwide epidemic. The objective of this study was to describe the demographics and clinical characteristics of suspected chikungunya cases. Chikungunya infection was confirmed by enzyme-linked immunosorbent assay and 548 patients where included in the study. Of these patients, 295 were positive for antibodies against chikungunya (53.8%), and 27.6% (151/295) were symptomatic for chikungunya infection, with a symptomatic:asymptomatic ratio of 1.04:1. Factors associated with infection included low income and low socio-economic strata (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.0-3.2, p = 0.003 and OR: 2.1; CI: 1.3-3.4, p = 0.002, respectively). Confirmed symptomatic cases were associated with symmetric arthritis (OR: 11.7; CI: 6.0-23.0, p < 0.001) of ankles (OR: 8.5; CI: 3.5-20.9, p < 0.001), hands (OR: 8.5; CI: 3.5-20.9, p < 0.001), feet (OR: 6.5; CI: 2.8-15.3, p < 0.001), and wrists (OR: 17.3; CI: 2.3-130.5, p < 0.001). Our study showed that poverty is associated with chikungunya infection. Public health strategies to prevent and control chikungunya should focus on poorer communities that are more vulnerable to infection. The rate of asymptomatic infections among confirmed cases was 48.8%. However, those with symptoms displayed a characteristic rheumatic clinical picture, which could help differentiate chikungunya infection from other endemic viral diseases.

    更新日期:2019-11-01
  • GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-22
    Danying Chen,Zhifei Hou,Dong Jiang,Mei Zheng,Guoli Li,Yue Zhang,Rui Li,Hanxin Lin,Jinhong Chang,Hui Zeng,Ju-Tao Guo,Xuesen Zhao

    Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.

    更新日期:2019-11-01
  • The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-22
    Tong-Yun Wang,Qiong-Qiong Fang,Feng Cong,Yong-Gang Liu,Hai-Ming Wang,Hong-Liang Zhang,Zhi-Jun Tian,Yan-Dong Tang,Xue-Hui Cai

    As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.

    更新日期:2019-11-01
  • Plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from food-producing animals, China, 2008-2018.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-22
    Chengtao Sun,Mingquan Cui,Shan Zhang,Hejia Wang,Li Song,Chunping Zhang,Qi Zhao,Dejun Liu,Yang Wang,Jianzhong Shen,Shixin Xu,Congming Wu

    The recent emergence of plasmid-mediated tigecycline resistance genes, tet(X3) and tet(X4), in animals and humans in China would pose a foreseeable threat to public health. To illustrate this paradigm shift in tigecycline resistance, here, covering the period 2008-2018, we retrospectively analysed a national strain collection of Escherichia coli (n = 2254), obtained from chickens and pigs, in six representative provinces of China. The gene tet(X4) was identified in five pig isolates collected in 2016 and 2018 from the provinces of Sichuan (3/15, 2018), Henan (1/25, 2018) and Guangdong (1/28, 2016), but not in the isolates prior to 2016. None of the isolates was detected harbouring tet(X3). All tet(X4)-positive E. coli exhibited high levels of tigecycline resistance (MICs, 16-64 mg/L), and two were confirmed as colistin resistant, harbouring chromosome-borne mcr-1 gene. The gene tet(X4) was detected on a plasmid in all five isolates, whereas a co-location of tet(X4) on the chromosome of one isolate was observed. Diverse host strains and novel plasmids related to the tet(X4) gene were observed. Our timely findings of the recent emergence of tet(X4) gene in food animal support the rapid surveillance and eradication of this gene before it is established.

    更新日期:2019-11-01
  • Molecular surveillance of antimicrobial resistance and transmission pattern of Mycobacterium leprae in Chinese leprosy patients.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-18
    Santosh Chokkakula,Zhiming Chen,Le Wang,Haiqin Jiang,Yanqing Chen,Ying Shi,Wenyue Zhang,Wei Gao,Jun Yang,Jinlan Li,Xiong Li,Tiejun Shui,Jun He,Limei Shen,Jie Liu,De Wang,Hao Wang,Huan Chen,Yanfei Kuang,Bin Li,Ziyi Chen,Aiping Wu,Meiwen Yu,Liangbin Yan,Naveen Chandra Suryadevara,Varalakshmi Vissa,Weida Liu,Hongsheng Wang

    Reports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI-0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.

    更新日期:2019-11-01
  • Insights into species-specific regulation of ANP32A on the mammalian-restricted influenza virus polymerase activity.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-15
    Zhenwei Bi,Hongliu Ye,Xingbo Wang,An Fang,Tianqi Yu,Liping Yan,Jiyong Zhou

    The ANP32A is responsible for mammalian-restricted influenza virus polymerase activity. However, the mechanism of ANP32A modulation of polymerase activity remains poorly understood. Here, we report that chicken ANP32A (chANP32A) -X1 and -X2 stimulated mammalian-restricted PB2 627E polymerase activity in a dose-dependent manner. Distinct effects of ANP32A constructs suggested that the 180VK181 residues within chANP32A-X1 are necessary but not sufficient to stimulate PB2 627E polymerase activity. The PB2 N567D, T598V, A613V or F636L mutations promoted PB2 627E polymerase activity and chANP32A-X1 showed additive effects, providing further support that species-specific regulation of ANP32A might be only relevant with the PB2 E627K mutation. Rescue of cycloheximide-mediated inhibition showed that ANP32A is species-specific for modulation of vRNA but not mRNA and cRNA, demonstrating chANP32A-X1 compensated for defective cRNPs produced by PB2 627E virus in mammalian cells. The promoter mutations of cRNA enhanced the restriction of PB2 627E polymerase in mammalian cells, which could be restored by chANP32A-X1, indicating that ANP32A is likely to regulate the interaction of viral polymerase with RNA promoter. Coimmunoprecipitation showed that ANP32A did not affect the primary cRNPs assembly. We propose a model that chANP32A-X1 regulates PB2 627E polymerase for suitable interaction with cRNA promoter for vRNA replication.

    更新日期:2019-11-01
  • Novel reassortant of H1N1 swine influenza virus detected in pig population in Russia.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-12
    Ivan Sobolev,Olga Kurskaya,Sergey Leonov,Marsel Kabilov,Tatyana Alikina,Alexander Alekseev,Yuriy Yushkov,Takehiko Saito,Yuko Uchida,Junki Mine,Alexander Shestopalov,Kirill Sharshov

    Pigs play an important role in interspecies transmission of the influenza virus, particularly as "mixing vessels" for reassortment. Two influenza A/H1N1 virus strains, A/swine/Siberia/1sw/2016 and A/swine/Siberia/4sw/2017, were isolated during a surveillance of pigs from private farms in Russia from 2016 to 2017. There was a 10% identity difference between the HA and NA nucleotide sequences of isolated strains and the most phylogenetically related sequences (human influenza viruses of 1980s). Simultaneously, genome segments encoding internal proteins were found to be phylogenetically related to the A/H1N1pdm09 influenza virus. In addition, two amino acids (129-130) were deleted in the HA of A/swine/Siberia/4sw/2017 compared to that of A/swine/Siberia/1sw/2016 HA.

    更新日期:2019-11-01
  • A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-10
    Zhenjie Zhang,Xingcheng Zhang,Michael J Carr,Hong Zhou,Juan Li,Shaoqiong Liu,Tao Liu,Weijia Xing,Weifeng Shi

    Coxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.

    更新日期:2019-11-01
  • Human testicular organoid system as a novel tool to study Zika virus pathogenesis.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2018-05-10
    Daniel P Strange,Nima Pourhabibi Zarandi,Goral Trivedi,Anthony Atala,Colin E Bishop,Hooman Sadri-Ardekani,Saguna Verma

    更新日期:2019-11-01
  • Biodiversity of rodent anelloviruses in China.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2018-03-22
    Jiang Du,Yuhui Li,Liang Lu,Dandan Zheng,Bo Liu,Li Yang,Haoxiang Su,Jie Dong,Lilian Sun,Yafang Zhu,Jian Yang,Fan Yang,Xiaobing Zhang,Qiyong Liu,Zhiqiang Wu,Qi Jin

    更新日期:2019-11-01
  • Tackling imported tropical diseases in China.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2018-02-08
    Xiao-Nong Zhou,Men-Bao Qian,Gerardo Priotto,José Ramón Franco,Jia-Gang Guo

    更新日期:2019-11-01
  • Enterovirus D68-associated respiratory and neurological illness in Spain, 2014-2018.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-10-02
    Rubén González-Sanz,Irene Taravillo,Jordi Reina,Ana Navascués,Antonio Moreno-Docón,Maitane Aranzamendi,María Pilar Romero,Margarita Del Cuerpo,Carmen Pérez-González,Sonia Pérez-Castro,Almudena Otero,María Cabrerizo

    During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. A total of 546 EV-positive samples from hospitalized patients with respiratory infections were included. EV-D68 was the most frequently detected type (46.6%, 191/410 typed EV). Other EV from species A (25.1%), B (27.8%) and C (0.5%) were also identified. EV-D68 infections were more associated with bronchitis while EV-A/B types were more frequent in upper respiratory illness (p < 0.01). EV-D68 was also detected in patients with neurological symptoms (nine meningitis/meningoencephalitis and eight acute flaccid paralysis cases). Phylogenetic analysis of 3'-VP1 region showed most Spanish EV-D68 sequences from 2014 to 2016 belonged to subclades B2/B3, as other American and European strains circulating during the same period. However, those detected in 2017 and 2018 clustered to the emerged subclade D1. In summary, different EV can cause respiratory infections but EV-D68 was the most prevalent, with several strains circulating in Spain at least since 2014. Association between EV-D68 infection and neurological disease was also described.

    更新日期:2019-11-01
  • MDCK-B4GalNT2 cells disclose a α2,3-sialic acid requirement for the 2009 pandemic H1N1 A/California/04/2009 and NA aid entry of A/WSN/33.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-29
    Ho Him Wong,Kevin Fung,John M Nicholls

    Switching of receptor binding preference has been widely considered as one of the necessary mutations for avian influenza viruses, enabling efficient transmissions between human hosts. By stably overexpressing B4GalNT2 gene in MDCK cells, surface α2,3-siallylactose receptors were modified without affecting α2,6-receptor expression. The cell line MDCK-B4GalNT2 was used as a tool to screen for α2,3-receptor requirements in a panel of influenza viruses with previously characterized glycan array data. Infection of viruses with α2,3-receptor binding capability was inhibited in MDCK-B4GalNT2 cells, with the exception of A/WSN/33 (WSN). Infection with the 2009 pandemic H1N1 strains, A/California/04/2009 (Cal04) and A/Hong Kong/415742/2009 (HK09), despite showing α2,6-receptor binding, was also found to be inhibited. Further investigation showed that viral inhibition was due to a reduction in viral entry rate and viral attachment. Recombinant WSN virus with the neuraminidase (NA) gene swapped to A/Puerto Rico/8/1934 (PR8) and Cal04 resulted in a significant viral inhibition in MDCK-B4GalNT2 cells. With oseltamivir, the NA active site was found to be important for the replication results of WSN, but not Cal04.

    更新日期:2019-11-01
  • The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the in vivo survival of vibrio vulnificus.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-24
    Wenzhi Tan,Kwangjoon Jeong,Raghunath Pendru,Sao Puth,Seol Hee Hong,Shee Eun Lee,Joon Haeng Rhee

    Vibrio vulnificus is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, V. vulnificus must adapt to redox fluctuations in vivo. In the present study, we show that deletion of V. vulnificus fexA gene caused hypersensitivity to acid and reactive oxygen species. The ΔfexA mutant exhibited severe in vivo survival defects. For deeper understanding the role of fexA gene on the successful V. vulnificus infection, we analyzed differentially expressed genes in ΔfexA mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the ΔfexA mutant under all three culture conditions. Among them, cydAB appeared to dominantly contribute to the defective phenotypes of the ΔfexA mutant. The fexA deletion induced compensatory point mutations in the cydAB promoter region over subcultures, suggesting essentiality. Those point mutations (PcydSMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the ΔfexA mutant. These results indicate that the cydAB operon, being regulated by FexA, plays a crucial role in V. vulnificus survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against V. vulnificus infection.

    更新日期:2019-11-01
  • Genomic epidemiology of Iranian Bordetella pertussis: 50 years after the implementation of whole cell vaccine.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-24
    Azadeh Safarchi,Sophie Octavia,Vajihe Sadat Nikbin,Masoumeh Nakhost Lotfi,Seyed Mohsen Zahraei,Chin Yen Tay,Binit Lamichhane,Fereshteh Shahcheraghi,Ruiting Lan

    Pertussis caused by Bordetella pertussis, remains a public health problem worldwide, despite high vaccine coverage in infants and children in many countries. Iran has been using whole cell vaccine for the last 50 years with more than 95% vaccination rate since 1988 and has experienced pertussis resurgence in recent years. Here, we sequenced 55 B. pertussis isolates mostly collected from three provinces with the highest number of pertussis cases in Iran, including Tehran, Mazandaran, and Eastern-Azarbayjan from the period of 2008-2016. Most isolates carried ptxP3/prn2 alleles (42/55, 76%), the same genotype as isolates circulating in acellular vaccine-administrating countries. The second most frequent genotype was ptxP3/prn9 (8/55, 14%). Only three isolates (5%) were ptxP1. Phylogenetic analysis showed that Iranian ptxP3 isolates can be divided into eight clades (Clades 1-8) with no temporal association. Most of the isolates from Tehran grouped together as one distinctive clade (Clade 8) with six unique single nucleotide polymorphisms (SNPs). In addition, the prn9 isolates were grouped together as Clade 5 with 12 clade-supporting SNPs. No pertactin deficient isolates were found among the 55 Iranian isolates. Our findings suggest that there is an ongoing adaptation and evolution of B. pertussis regardless of the types of vaccine used.

    更新日期:2019-11-01
  • Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-20
    Huijing Chen,Yi Zhang,Shuangshuang Ye,Qiong Wu,Youfen Lin,Kaiqin Sheng,Wannan Chen,Xinjian Lin,Xu Lin

    HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.

    更新日期:2019-11-01
  • Active surveillance and genetic evolution of avian influenza viruses in Egypt, 2016-2018.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-19
    Ahmed Kandeil,Joseph T Hicks,Sean G Young,Ahmed N El Taweel,Ahmed S Kayed,Yassmin Moatasim,Omnia Kutkat,Ola Bagato,Pamela P McKenzie,Zhipeng Cai,Rebecca Badra,Mohamed Kutkat,Justin Bahl,Richard J Webby,Ghazi Kayali,Mohamed A Ali

    Egypt is a hotspot for avian influenza virus (AIV) due to the endemicity of H5N1 and H9N2 viruses. AIVs were isolated from 329 samples collected in 2016-2018; 48% were H9N2, 37.1% were H5N8, 7.6% were H5N1, and 7.3% were co-infections with 2 of the 3 subtypes. The 32 hemagglutinin (HA) sequences of the H5N1 viruses formed a well-defined lineage within clade 2.2.1.2. The 10 HA sequences of the H5N8 viruses belonged to a subclade within 2.3.4.4. The 11 HA of H9N2 isolates showed high sequence homology with other Egyptian G1-like H9N2 viruses. The prevalence of H5N8 viruses in ducks (2.4%) was higher than in chickens (0.94%). Genetic reassortment was detected in H9N2 viruses. Antigenic analysis showed that H9N2 viruses are homogenous, antigenic drift was detected among H5N1 viruses. AI H5N8 showed higher replication rate followed by H9N2 and H5N1, respectively. H5N8 was more common in Southern Egypt, H9N2 in the Nile Delta, and H5N1 in both areas. Ducks and chickens played a significant role in transmission of H5N1 viruses. The endemicity and co-circulation of H5N1, H5N8, and H9N2 AIV coupled with the lack of a clear control strategy continues to provide avenues for further virus evolution in Egypt.

    更新日期:2019-11-01
  • An evolutionary divergent pestivirus lacking the Npro gene systemically infects a whale species.
    Emerg. Microbes Infect. (IF 6.212) Pub Date : 2019-09-19
    Wendy K Jo,Cornelis van Elk,Marco van de Bildt,Peter van Run,Monique Petry,Sonja T Jesse,Klaus Jung,Martin Ludlow,Thijs Kuiken,Albert Osterhaus

    Pestiviruses typically infect members of the order Artiodactyla, including ruminants and pigs, although putative rat and bat pestiviruses have also been described. In the present study, we identified and characterized an evolutionary divergent pestivirus in the toothed whale species, harbour porpoise (Phocoena phocoena). We tentatively named the virus Phocoena pestivirus (PhoPeV). PhoPeV displays a typical pestivirus genome organization except for the unique absence of Npro, an N-terminal autoprotease that targets the innate host immune response. Evolutionary evidence indicates that PhoPeV emerged following an interspecies transmission event from an ancestral pestivirus that expressed Npro. We show that 9% (n = 10) of stranded porpoises from the Dutch North Sea coast (n = 112) were positive for PhoPeV and they displayed a systemic infection reminiscent of non-cytopathogenic persistent pestivirus infection. The identification of PhoPeV extends the host range of pestiviruses to cetaceans (dolphins, whales, porpoises), which are considered to have evolved from artiodactyls (even-toed ungulates). Elucidation of the pathophysiology of PhoPeV infection and Npro unique absence will add to our understanding of molecular mechanisms governing pestivirus pathogenesis.

    更新日期:2019-11-01
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