-
Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Ingo Fohmann,Alina Weinmann,Fabian Schumacher,Simon Peters,Agata Prell,Cynthia Weigel,Sarah Spiegel,Burkhard Kleuser,Alexandra Schubert-Unkmeir
Invasion of brain endothelial cells (BECs) is central to the pathogenicity of Neisseria meningitidis infection. Here, we established a key role for the bioactive sphingolipid sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) 2 in the uptake process. Quantitative sphingolipidome analyses of BECs infected with N. meningitidis revealed elevated S1P levels, which could be attributed to enhanced expression
-
Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Raffael Júnio Araújo de Castro,Clara Luna Marina,Aude Sturny-Leclère,Christian Hoffmann,Pedro Henrique Bürgel,Sarah Sze Wah Wong,Vishukumar Aimanianda,Hugo Varet,Ruchi Agrawal,Anamélia Lorenzetti Bocca,Alexandre Alanio
Macrophages play a key role in disseminated cryptococcosis, a deadly fungal disease caused by Cryptococcus neoformans. This opportunistic infection can arise following the reactivation of a poorly characterized latent infection attributed to dormant C. neoformans. Here, we investigated the mechanisms underlying reactivation of dormant C. neoformans using an in vitro co-culture model of viable but non-culturable
-
Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Jing Yang,Sheng Lin,Zimin Chen,Fanli Yang,Liyan Guo,Lingling Wang,Yanping Duan,Xindan Zhang,Yushan Dai,Keqing Yin,Chongzhang Yu,Xin Yuan,Honglu Sun,Bin He,Yu Cao,Haoyu Ye,Haohao Dong,Xianbo Liu,Bo Chen,Jian Li,Qi Zhao,Guangwen Lu
The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and
-
The RNA world of fungal pathogens. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Srimeenakshi Sankaranarayanan,Seomun Kwon,Kai Heimel,Michael Feldbrügge
-
Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Jianing Wang,Zhimin Duan,Rong Zeng,Lu Yang,Weizhao Liu,Yiman Liu,Qian Yao,Xu Chen,Ling-Juan Zhang,Min Li
Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions
-
Preferential selection of viral escape mutants by CD8+ T cell 'sieving' of SIV reactivation from latency. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-30 Steffen S Docken,Kevin McCormick,M Betina Pampena,Sadia Samer,Emily Lindemuth,Mykola Pinkevych,Elise G Viox,Yuhuang Wu,Timothy E Schlub,Deborah Cromer,Brandon F Keele,Mirko Paiardini,Michael R Betts,Katharine J Bar,Miles P Davenport
HIV rapidly rebounds after interruption of antiretroviral therapy (ART). HIV-specific CD8+ T cells may act to prevent early events in viral reactivation. However, the presence of viral immune escape mutations may limit the effect of CD8+ T cells on viral rebound. Here, we studied the impact of CD8 immune pressure on post-treatment rebound of barcoded SIVmac293M in 14 Mamu-A*01 positive rhesus macaques
-
Neuropilin-1 identifies a subset of highly activated CD8+ T cells during parasitic and viral infections. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-29 Hanna Abberger,Matthias Hose,Anne Ninnemann,Christopher Menne,Mareike Eilbrecht,Karl S Lang,Kai Matuschewski,Robert Geffers,Josephine Herz,Jan Buer,Astrid M Westendorf,Wiebke Hansen
Neuropilin-1 (Nrp-1) expression on CD8+ T cells has been identified in tumor-infiltrating lymphocytes and in persistent murine gamma-herpes virus infections, where it interferes with the development of long-lived memory T cell responses. In parasitic and acute viral infections, the role of Nrp-1 expression on CD8+ T cells remains unclear. Here, we demonstrate a strong induction of Nrp-1 expression
-
A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-29 Ashok K Dwivedi,Germán G Gornalusse,David A Siegel,Alton Barbehenn,Cassandra Thanh,Rebecca Hoh,Kristen S Hobbs,Tony Pan,Erica A Gibson,Jeffrey Martin,Frederick Hecht,Christopher Pilcher,Jeffrey Milush,Michael P Busch,Mars Stone,Meei-Li Huang,Julieta Reppetti,Phuong M Vo,Claire N Levy,Pavitra Roychoudhury,Keith R Jerome,Florian Hladik,Timothy J Henrich,Steven G Deeks,Sulggi A Lee
The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells
-
A chemosensory-like histidine kinase is dispensable for chemotaxis in vitro but regulates the virulence of Borrelia burgdorferi through modulating the stability of RpoS. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-27 Ching Wooen Sze,Kai Zhang,Michael J Lynch,Radha Iyer,Brian R Crane,Ira Schwartz,Chunhao Li
As an enzootic pathogen, the Lyme disease bacterium Borrelia burgdorferi possesses multiple copies of chemotaxis proteins, including two chemotaxis histidine kinases (CHK), CheA1 and CheA2. Our previous study showed that CheA2 is a genuine CHK that is required for chemotaxis; however, the role of CheA1 remains mysterious. This report first compares the structural features that differentiate CheA1 and
-
Conserved antigen structures and antibody-driven variations on foot-and-mouth disease virus serotype A revealed by bovine neutralizing monoclonal antibodies. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-20 Kun Li,Yong He,Li Wang,Pinghua Li,Huifang Bao,Shulun Huang,Shasha Zhou,Guoqiang Zhu,Yali Song,Ying Li,Sheng Wang,Qianliang Zhang,Pu Sun,Xingwen Bai,Zhixun Zhao,Zhiyong Lou,Yimei Cao,Zengjun Lu,Zaixin Liu
Foot-and-mouth disease virus (FMDV) serotype A is antigenically most variable within serotypes. The structures of conserved and variable antigenic sites were not well resolved. Here, a historical A/AF72 strain from A22 lineage and a latest A/GDMM/2013 strain from G2 genotype of Sea97 lineage were respectively used as bait antigen to screen single B cell antibodies from bovine sequentially vaccinated
-
Arabidopsis eIF4E1 protects the translational machinery during TuMV infection and restricts virus accumulation. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-20 Delyan Zafirov,Nathalie Giovinazzo,Cécile Lecampion,Ben Field,Julia Novion Ducassou,Yohann Couté,Karen S Browning,Christophe Robaglia,Jean-Luc Gallois
Successful subversion of translation initiation factors eIF4E determines the infection success of potyviruses, the largest group of viruses affecting plants. In the natural variability of many plant species, resistance to potyvirus infection is provided by polymorphisms at eIF4E that renders them inadequate for virus hijacking but still functional in translation initiation. In crops where such natural
-
Direct and biologically significant interactions of human herpesvirus 8 interferon regulatory factor 1 with STAT3 and Janus kinase TYK2. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-20 Zunlin Yang,Qiwang Xiang,John Nicholas
Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRFs) that target cellular IRFs and/or other innate-immune and stress signaling regulators and suppress the cellular response to viral infection and replication. For vIRF-1, cellular protein targets include IRFs, p53, p53-activating ATM kinase, BH3-only proteins, and antiviral signaling effectors MAVS and STING; vIRF-1 inhibits
-
A small molecule exerts selective antiviral activity by targeting the human cytomegalovirus nuclear egress complex. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-17 Han Chen,Ming F Lye,Christoph Gorgulla,Scott B Ficarro,Gregory D Cuny,David A Scott,Fan Wu,Paul W Rothlauf,Xiaoou Wang,Rosio Fernandez,Jean M Pesola,Sorin Draga,Jarrod A Marto,James M Hogle,Haribabu Arthanari,Donald M Coen
Human cytomegalovirus (HCMV) is an important pathogen for which new antiviral drugs are needed. HCMV, like other herpesviruses, encodes a nuclear egress complex (NEC) composed of two subunits, UL50 and UL53, whose interaction is crucial for viral replication. To explore whether small molecules can exert selective antiviral activity by inhibiting NEC subunit interactions, we established a homogeneous
-
The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-15 Belén Carriquí-Madroñal,Julie Sheldon,Mara Duven,Cora Stegmann,Karsten Cirksena,Emanuel Wyler,Francisco J Zapatero-Belinchón,Florian W R Vondran,Gisa Gerold
Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological
-
Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-13 Shiromani Jayawardhana,Alexander I Ward,Amanda F Francisco,Michael D Lewis,Martin C Taylor,John M Kelly,Francisco Olmo
Benznidazole is the front-line drug used to treat infections with Trypanosoma cruzi, the causative agent of Chagas disease. However, for reasons that are unknown, treatment failures are common. When we examined parasites that survived benznidazole treatment in mice using highly sensitive in vivo and ex vivo bioluminescence imaging, we found that recrudescence is not due to persistence of parasites
-
SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-13 Xiaolin Zhang,Ziwei Yang,Ting Pan,Qinqin Sun,Qingyang Chen,Pei-Hui Wang,Xiaojuan Li,Ersheng Kuang
Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/β, subsequently leading to IRF3 and NF-κB phosphorylation. However
-
Evasion of host antioxidative response via disruption of NRF2 signaling in fatal Ehrlichia-induced liver injury. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-13 Aditya Kumar Sharma,Abdeljabar El Andaloussi,Nahed Ismail
Ehrlichia is Gram negative obligate intracellular bacterium that cause human monocytotropic ehrlichiosis (HME). HME is characterized by acute liver damage and inflammation that may progress to fatal toxic shock. We previously showed that fatal ehrlichiosis is due to deleterious activation of inflammasome pathways, which causes excessive inflammation and liver injury. Mammalian cells have developed
-
A sporulation signature protease is required for assembly of the spore surface layers, germination and host colonization in Clostridioides difficile. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-13 Eleonora Marini,Carmen Olivença,Sara Ramalhete,Andrea Martinez Aguirre,Patrick Ingle,Manuel N Melo,Wilson Antunes,Nigel P Minton,Guillem Hernandez,Tiago N Cordeiro,Joseph A Sorg,Mónica Serrano,Adriano O Henriques
A genomic signature for endosporulation includes a gene coding for a protease, YabG, which in the model organism Bacillus subtilis is involved in assembly of the spore coat. We show that in the human pathogen Clostridioidesm difficile, YabG is critical for the assembly of the coat and exosporium layers of spores. YabG is produced during sporulation under the control of the mother cell-specific regulators
-
Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-10 Lijuan Bao,Hao Sun,Yihong Zhao,Lianjun Feng,Keyi Wu,Shan Shang,Jiawen Xu,Ruping Shan,Shiyu Duan,Min Qiu,Naisheng Zhang,Xiaoyu Hu,Caijun Zhao,Yunhe Fu
Subacute ruminal acidosis (SARA) has been demonstrated to promote the development of mastitis, one of the most serious diseases in dairy farming worldwide, but the underlying mechanism is unclear. Using untargeted metabolomics, we found hexadecanamide (HEX) was significantly reduced in rumen fluid and milk from cows with SARA-associated mastitis. Herein, we aimed to assess the protective role of HEX
-
Insights and advances in recurrent vulvovaginal candidiasis. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-10 Javier San Juan Galán,Vanessa Poliquin,Aleeza Cara Gerstein
-
Antibody-mediated spike activation promotes cell-cell transmission of SARS-CoV-2. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-10 Shi Yu,Xu Zheng,Yanqiu Zhou,Yuhui Gao,Bingjie Zhou,Yapei Zhao,Tingting Li,Yunyi Li,Jiabin Mou,Xiaoxian Cui,Yuying Yang,Dianfan Li,Min Chen,Dimitri Lavillette,Guangxun Meng
The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is
-
Effects of N-glycan modifications on spike expression, virus infectivity, and neutralization sensitivity in ancestral compared to Omicron SARS-CoV-2 variants. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-09 Sabrina Lusvarghi,Charles B Stauft,Russell Vassell,Brittany Williams,Haseebullah Baha,Wei Wang,Sabari Nath Neerukonda,Tony Wang,Carol D Weiss
The SARS-CoV-2 spike glycoprotein has 22 potential N-linked glycosylation sites per monomer that are highly conserved among diverse variants, but how individual glycans affect virus entry and neutralization of Omicron variants has not been extensively characterized. Here we compared the effects of specific glycan deletions or modifications in the Omicron BA.1 and D614G spikes on spike expression, processing
-
COVID-19: A complex disease with a unique metabolic signature. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-09 Veronica Ghini,Walter Vieri,Tommaso Celli,Valentina Pecchioli,Nunzia Boccia,Tania Alonso-Vásquez,Lorenzo Pelagatti,Marco Fondi,Claudio Luchinat,Laura Bertini,Vieri Vannucchi,Giancarlo Landini,Paola Turano
Plasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display
-
The biological functions of sphingolipids in plant pathogenic fungi. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-09 Xue-Ming Zhu,Lin Li,Jian-Dong Bao,Jiao-Yu Wang,Asen Daskalov,Xiao-Hong Liu,Maurizio Del Poeta,Fu-Cheng Lin
Sphingolipids are critically significant in a range of biological processes in animals, plants, and fungi. In mammalian cells, they serve as vital components of the plasma membrane (PM) in maintaining its structure, tension, and fluidity. They also play a key role in a wide variety of biological processes, such as intracellular signal transduction, cell polarization, differentiation, and migration
-
Cryo-electron tomography reveals the binding and release states of the major adhesion complex from Mycoplasma genitalium. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-08 Lasse Sprankel,Margot P Scheffer,Sina Manger,Utz H Ermel,Achilleas S Frangakis
The nap particle is an immunogenic surface adhesion complex from Mycoplasma genitalium. It is essential for motility and responsible for binding sialylated oligosaccharides on the surface of the host cell. The nap particle is composed of two P140-P110 heterodimers, the structure of which was recently solved. However, the interpretation of the mechanism by which the mycoplasma cells orchestrate adhesion
-
Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-08 Grace P Carreno-Florez,Brian R Kocak,Matthew R Hendricks,Jeffrey A Melvin,Katrina B Mar,Jessica Kosanovich,Rachel L Cumberland,Greg M Delgoffe,Sruti Shiva,Kerry M Empey,John W Schoggins,Jennifer M Bomberger
Clinical studies report that viral infections promote acute or chronic bacterial infections at multiple host sites. These viral-bacterial co-infections are widely linked to more severe clinical outcomes. In experimental models in vitro and in vivo, virus-induced interferon responses can augment host susceptibility to secondary bacterial infection. Here, we used a cell-based screen to assess 389 interferon-stimulated
-
Inflammasome-triggered IL-18 controls skin inflammation in the progression of Buruli ulcer. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-01 Toshihiko Suzuki,Kotchakorn Boonyaleka,Tokuju Okano,Tamako Iida,Mitsunori Yoshida,Hanako Fukano,Yoshihiko Hoshino,Yoichiro Iwakura,Anthony S Ablordey,Hiroshi Ashida
Buruli ulcer is an emerging chronic infectious skin disease caused by Mycobacterium ulcerans. Mycolactone, an exotoxin produced by the bacterium, is the only identified virulence factor so far, but the functions of this toxin and the mechanisms of disease progression remain unclear. By interfering Sec61 translocon, mycolactone inhibits the Sec61-dependent co-translational translocation of newly synthesized
-
Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals. PLOS Pathog. (IF 6.7) Pub Date : 2023-11-01 Sana Eybpoosh,Alireza Biglari,Rahim Sorouri,Fatemeh Ashrafian,Mona Sadat Larijani,Vicente Verez-Bencomo,Maria Eugenia Toledo-Romani,Carmen Valenzuela Silva,Mostafa Salehi-Vaziri,Sarah Dahmardeh,Delaram Doroud,Mohammad Banifazl,Ehsan Mostafavi,Anahita Bavand,Amitis Ramezani
BACKGROUND This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into
-
The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-31 Manali M Kamath,Jorge D Lightfoot,Emily M Adams,Ryan M Kiser,Becca L Wells,Kevin K Fuller
The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates the mRNA of the transcription factor HacA. Spliced hacA accumulates under conditions of acute ER stress in vitro, and UPR null mutants are hypovirulent in a murine model of invasive pulmonary infection. In this report, we demonstrate that a hacA deletion
-
Sugarcane streak mosaic virus P1 protein inhibits unfolded protein response through direct suppression of bZIP60U splicing. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Kun Zhang,Tianxiao Gu,Xiaowei Xu,Haifeng Gan,Lang Qin,Chenwei Feng,Zhen He
The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the
-
Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Wei-Xin Chin,Hao Yuin Kong,Isabelle Xin Yu Zhu,Zi Yun Teo,Regina Faruk,Regina Ching Hua Lee,Si Xian Ho,Zhen Qin Aw,Bowen Yi,Xin Jun Hou,Antson Kiat Yee Tan,Thinesshwary Yogarajah,Roland G Huber,Yu Cai,Yue Wan,Justin Jang Hann Chu
Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal
-
Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Anna Malyshkina,Wibke Bayer,Philip Podschwadt,Lucas Otto,Zehra Karakoese,Kathrin Sutter,Kirsten Bruderek,Baoxiao Wang,Kerry J Lavender,Mario L Santiago,Pia Madeleine Leipe,Carina Elsner,Stefan Esser,Sven Brandau,Matthias Gunzer,Ulf Dittmer
Antiretroviral therapy (ART) transformed HIV from a life-threatening disease to a chronic condition. However, eliminating the virus remains an elusive therapy goal. For several decades, Friend virus (FV) infection serves as a murine model to study retrovirus immunity. Similar to HIV, FV persists at low levels in lymph nodes B cell follicles avoiding elimination by immune cells. Such immune-privileged
-
Virally encoded interleukin-6 facilitates KSHV replication in monocytes and induction of dysfunctional macrophages. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Michiko Shimoda,Tomoki Inagaki,Ryan R Davis,Alexander Merleev,Clifford G Tepper,Emanual Maverakis,Yoshihiro Izumiya
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of Kaposi's sarcoma and hyperinflammatory lymphoproliferative disorders. Understanding the mechanism by which KSHV increases the infected cell population is crucial for curing KSHV-associated diseases. Using scRNA-seq, we demonstrate that KSHV preferentially infects CD14+ monocytes, sustains
-
The intriguing phenomenon of cross-kingdom infections of plant and insect viruses to fungi: Can other animal viruses also cross-infect fungi? PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Ida Bagus Andika,Xinran Cao,Hideki Kondo,Liying Sun
Fungi are highly widespread and commonly colonize multicellular organisms that live in natural environments. Notably, studies on viruses infecting plant-associated fungi have revealed the interesting phenomenon of the cross-kingdom transmission of viruses and viroids from plants to fungi. This implies that fungi, in addition to absorbing water, nutrients, and other molecules from the host, can acquire
-
The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Megan Okada,Paul A Sigala
Isoprenoid precursor synthesis is an ancient and fundamental function of plastid organelles and a critical metabolic activity of the apicoplast in Plasmodium malaria parasites [1-3]. Over the past decade, our understanding of apicoplast properties and functions has increased enormously [4], due in large part to our ability to rescue blood-stage parasites from apicoplast-specific dysfunctions by supplementing
-
Prion propagation and cellular dysfunction in prion disease: Disconnecting the dots. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-26 Simote T Foliaki,Cathryn L Haigh
-
High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-25 Rohini Mopuri,Sarah Welbourn,Tysheena Charles,Pooja Ralli-Jain,David Rosales,Samantha Burton,Areeb Aftab,Kirti Karunakaran,Kathryn Pellegrini,William Kilembe,Etienne Karita,Sandrasegaram Gnanakaran,Amit A Upadhyay,Steven E Bosinger,Cynthia A Derdeyn
A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing
-
Tyrosine phosphorylation of IRF3 by BLK facilitates its sufficient activation and innate antiviral response. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-23 Wei-Wei Li,Xu-Xu Fan,Zi-Xiang Zhu,Xue-Jing Cao,Zhao-Yu Zhu,Dan-Shi Pei,Yi-Zhuo Wang,Ji-Yan Zhang,Yan-Yi Wang,Hai-Xue Zheng
Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect
-
Innate lymphoid cells-Underexplored guardians of immunity. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-19 Irina Tsymala,Karl Kuchler
-
Know the enemy and know yourself: Addressing cryptic fungal pathogens of humans and beyond. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-19 Jacob L Steenwyk,Antonis Rokas,Gustavo H Goldman
-
Intestinal injury and the gut microbiota in patients with Plasmodium falciparum malaria. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-19 Natthida Sriboonvorakul,Kesinee Chotivanich,Udomsak Silachamroon,Weerapong Phumratanaprapin,John H Adams,Arjen M Dondorp,Stije J Leopold
The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding parasite-induced intestinal injury and changes in the human intestinal microbiota composition in patients with Plasmodium falciparum malaria. During the blood stage of P. falciparum infection, infected red blood cells adhere to the vascular
-
Tools and techniques to identify, study, and control Candida auris. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-19 James Carty,Anuradha Chowdhary,Douglas Bernstein,Shankar Thangamani
Candida auris, is an emerging fungal pathogen that can cause life-threatening infections in humans. Unlike many other Candida species that colonize the intestine, C. auris most efficiently colonizes the skin. Such colonization contaminates the patient's environment and can result in rapid nosocomial transmission. In addition, this transmission can lead to outbreaks of systemic infections that have
-
A regulatory role for the redox status of the pepino mosaic virus coat protein. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-18 Eduardo Méndez-López,Miguel A Aranda
Cysteine oxidations play important regulatory roles during animal virus infections. Despite the importance of redox modifications during plant infections, no plant virus protein has yet been shown to be regulated by cysteine oxidation. The potexvirus pepino mosaic virus (PepMV) is pandemic in tomato crops. Previously we modeled the structure of the PepMV particle and coat protein (CP) by cryo-electron
-
Serpin-1a and serpin-6 regulate the Toll pathway immune homeostasis by synergistically inhibiting the Spätzle-processing enzyme CLIP2 in silkworm, Bombyx mori. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-18 Huawei Liu,Jiahui Xu,Luoling Wang,Pengchao Guo,Zhangchen Tang,Xiaotong Sun,Xin Tang,Wei Wang,Lingyan Wang,Yang Cao,Qingyou Xia,Ping Zhao
The Toll receptor signaling pathway is an important innate immune response of insects to pathogen infection; its extracellular signal transduction involves serine protease cascade activation. However, excessive or constitutive activation of the Toll pathway can be detrimental. Hence, the balance between activation and inhibition of the extracellular protease cascade must be tightly regulated to achieve
-
Preexisting helminth challenge exacerbates infection and reactivation of gammaherpesvirus in tissue resident macrophages. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-17 Christina M Zarek,Chaitanya Dende,Jaime Coronado,Mihir Pendse,Phillip Dryden,Lora V Hooper,Tiffany A Reese
Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the
-
SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-16 Lieve E H van der Donk,Marta Bermejo-Jambrina,John L van Hamme,Mette M W Volkers,Ad C van Nuenen,Neeltje A Kootstra,Teunis B H Geijtenbeek
SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory responses are a major factor in causing morbidity and mortality, superinfections with bacteria during severe COVID-19 often cause pneumonia, bacteremia and sepsis. Aberrant immune responses might underlie increased sensitivity to bacteria
-
Introducing Short Reports-A new platform for swiftly communicating research findings. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-16 Julia Squarr
-
Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-13 Hua Chen,Sheng Lin,Fanli Yang,Zimin Chen,Liyan Guo,Jing Yang,Xi Lin,Lingling Wang,Yanping Duan,Ao Wen,Xindan Zhang,Yushan Dai,Keqing Yin,Xin Yuan,Chongzhang Yu,Yarong He,Bin He,Yu Cao,Haohao Dong,Jian Li,Qi Zhao,Quan Liu,Guangwen Lu
Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and
-
Mechanistic insights into the interaction between the host gut microbiome and malaria. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-12 Rabindra K Mandal,Nathan W Schmidt
Malaria is a devastating infectious disease and significant global health burden caused by the bite of a Plasmodium-infected female Anopheles mosquito. Gut microbiota was recently discovered as a risk factor of severe malaria. This review entails the recent advances on the impact of gut microbiota composition on malaria severity and consequence of malaria infection on gut microbiota in mammalian hosts
-
Grapevine red blotch disease: A comprehensive Q&A guide. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-12 Björn Krenz,Marc Fuchs,Jeremy R Thompson
-
Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-11 Manman Dai,Sufang Zhu,Zhihao An,Bowen You,Ziwei Li,Yongxiu Yao,Venugopal Nair,Ming Liao
Chicken lung is an important target organ of avian influenza virus (AIV) infection, and different pathogenic virus strains lead to opposite prognosis. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of 16 cell types (19 clusters) in the lung tissue of chickens infected with H5N1 highly pathogenic avian influenza virus (HPAIV) and H9N2
-
Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-11 Gergana Taleva,Michaela Husová,Brian Panicucci,Carolina Hierro-Yap,Erika Pineda,Marc Biran,Martin Moos,Petr Šimek,Falk Butter,Frédéric Bringaud,Alena Zíková
The long slender bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (ΔΨm) through the proton-pumping activity of the FoF1-ATP synthase operating in the reverse mode. The ATP that drives this hydrolytic reaction has long been thought to be generated by glycolysis and imported from the cytosol via an ATP/ADP carrier (AAC). Indeed, we demonstrate that AAC is the
-
N-linked glycosylation of flavivirus E protein contributes to viral particle formation. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-11 Kotaro Ishida,Hirokazu Yagi,Yukinari Kato,Eiji Morita
In the case of the Japanese encephalitis virus (JEV), the envelope protein (E), a major component of viral particles, contains a highly conserved N-linked glycosylation site (E: N154). Glycosylation of the E protein is thought to play an important role in the ability of the virus to attach to target cells during transmission; however, its role in viral particle formation and release remains poorly
-
Editorial Note: Viral-mediated activation and inhibition of programmed cell death. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-10
-
Phenotype and fate of liver-resident CD8 T cells during acute and chronic hepacivirus infection. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-09 Piyush Dravid,Satyapramod Murthy,Zayed Attia,Cole Cassady,Rahul Chandra,Sheetal Trivedi,Ashish Vyas,John Gridley,Brantley Holland,Anuradha Kumari,Arash Grakoui,John M Cullen,Christopher M Walker,Himanshu Sharma,Amit Kapoor
Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J
-
The hybrid RAVE complex plays V-ATPase-dependent and -independent pathobiological roles in Cryptococcus neoformans. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-09 Jin-Tae Choi,Yeseul Choi,Yujin Lee,Seung-Heon Lee,Seun Kang,Kyung-Tae Lee,Yong-Sun Bahn
V-ATPase, which comprises 13-14 subunits, is essential for pH homeostasis in all eukaryotes, but its proper function requires a regulator to assemble its subunits. While RAVE (regulator of H+-ATPase of vacuolar and endosomal membranes) and Raboconnectin-3 complexes assemble V-ATPase subunits in Saccharomyces cerevisiae and humans, respectively, the function of the RAVE complex in fungal pathogens remains
-
Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-06 Mykola Pinkevych,Steffen S Docken,Afam A Okoye,Christine M Fennessey,Gregory Q Del Prete,Maria Pino,Justin L Harper,Michael R Betts,Mirko Paiardini,Brandon F Keele,Miles P Davenport
One approach to 'functional cure' of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral 'setpoint' level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124 total animals from 10 independent studies across 3
-
Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-06 Yang Wu,Mingwei Li,Jin Tian,Haoxin Yan,Yudi Pan,Hongyan Shi,Da Shi,Jianfei Chen,Longjun Guo,Li Feng
Coronaviruses (CoVs) are a family of the largest RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans, imposing great threats to the public safety and animal health. Porcine deltacoronavirus (PDCoV), a newly emerging enteropathogenic coronavirus, causes severe diarrhea in suckling piglets all over the world and poses potential risks of cross-species transmission
-
Prevention of zoonotic spillover: From relying on response to reducing the risk at source. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-05 ,Wanda Markotter,Thomas C Mettenleiter,Wiku B Adisasmito,Salama Almuhairi,Casey Barton Behravesh,Pépé Bilivogui,Salome A Bukachi,Natalia Casas,Natalia Cediel Becerra,Dominique F Charron,Abhishek Chaudhary,Janice R Ciacci Zanella,Andrew A Cunningham,Osman Dar,Nitish Debnath,Baptiste Dungu,Elmoubasher Farag,George F Gao,David T S Hayman,Margaret Khaitsa,Marion P G Koopmans,Catherine Machalaba,John S
-
Protective mechanisms of nonneutralizing antiviral antibodies. PLOS Pathog. (IF 6.7) Pub Date : 2023-10-05 Tawny L Chandler,Agnes Yang,Claire E Otero,Sallie R Permar,Sarah L Caddy
Antibodies that can bind to viruses but are unable to block infection in cell culture are known as "nonneutralizing antibodies." Such antibodies are nearly universally elicited following viral infection and have been characterized in viral infections such as influenza, rotavirus, cytomegalovirus, HIV, and SARS-CoV-2. It has been widely assumed that these nonneutralizing antibodies do not function in