Epidemiology of Pestivirus H in Brazil and Its Control Implications
Fernando V. Bauermann
Julia F. Ridpath- 1Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University (OSU), Stillwater, OK, United States
- 2Ridpath Consulting, LLC, Gilbert, IA, United States
Along with viruses in the Pestivirus A (Bovine Viral Diarrhea Virus 1, BVDV1) and B species (Bovine Viral Diarrhea Virus 2, BVDV2), members of the Pestivirus H are mainly cattle pathogens. Viruses belonging to the Pestivirus H group are known as HoBi-like pestiviruses (HoBiPev). Genetic and antigenic characterization suggest that HoBiPev are the most divergent pestiviruses identified in cattle to date. The phylogenetic analysis of HoBiPev results in at least five subgroups (a–e). Under natural or experimental conditions, calves infected with HoBiPev strains typically display mild upper respiratory signs, including nasal discharge and cough. Although BVDV1 and BVDV2 are widely distributed and reported in many South American countries, reports of HoBiPev in South America are mostly restricted to Brazil. Despite the endemicity and high prevalence of HoBiPev in Brazil, only HoBiPev-a was identified to date in Brazil. Unquestionably, HoBiPev strains in BVDV vaccine formulations are required to help curb HoBiPev spread in endemic regions. The current situation in Brazil, where at this point only HoBiPev-a seems present, provides a more significant opportunity to control these viruses with the use of a vaccine with a single HoBiPev subtype. Despite the lack of differentiation among bovine pestiviruses by current BVDV tests, the reduced genetic variability of HoBiPev in Brazil may allow reliable identification of cases within the region. On the other hand, introducing foreign ruminants, biologicals, and genetic material to South America, especially if it originated from other HoBiPev-endemic countries, should consider the risk of introducing divergent HoBiPev subtypes.
Introduction
Pestivirus H History Recap
The pestivirus genus within the family Flaviviridae underwent extensive taxonomic revisions in the past few years, leading to many of its members' classification or reclassification. For decades, only four viral species were officially recognized and historically known as Bovine Viral Diarrhea Virus 1 and 2 (BVDV1 and BVDV2), Classical Swine Fever Virus, and Border Disease Virus. These species are now classified as Pestivirus A, B, C, and D. Several pestiviruses described as “atypical” are currently officially recognized at the species level (1). The seven recently classified species are the Pestivirus E (Pronghorn pestivirus), Pestivirus F (Bungowannah virus), Pestivirus G (Giraffe pestivirus), Pestivirus H (HoBi-like pestivirus), Pestivirus I (Aydin-like pestivirus), Pestivirus J (rat pestivirus), and Pestivirus K (atypical porcine pestivirus) (2).
Among the new pestivirus species, Pestivirus H and K are likely the most widespread “new” species (3, 4). Both species have been reported in the American continent, Europe, and Asia (3, 4). Members of the Pestivirus K species were only described infecting pig (5), while Pestivirus H is mainly a bovine pathogen. However, natural infection with viruses from the Pestivirus H species has been described in small ruminant species in Asia and in water buffalos in Brazil and Argentina (6–10).
Pestivirus H was discovered in Germany in 2004 as a cell culture contaminant (11). At that time, the virus was designated as an atypical bovine pestivirus. The strain was named HoBi_D32/00, referencing the researchers, Horst and Birgit, who isolated and characterized the virus. The virus's origin was traced to a Brazilian fetal bovine serum (FBS) used as a media supplement for cell culture in that laboratory (11). The HoBi_D32/00 virus was first described as a putative new pestivirus species. Initially, group members were called atypical bovine pestivirus, BVDV3, or HoBi-like pestiviruses (HoBiPev) (12).
Studies comparing HoBiPev genetic and antigenic characteristics to those observed between BVDV1 (Pestivirus A) and BVDV2 (Pestivirus B) demonstrated that HoBiPev was the most divergent ruminant pestivirus identified to date (11, 13). The characterization of additional HoBiPev isolates strengthened the overall understanding of the genetic and antigenic differences between Pestivirus H, A, and B species and their implications toward the diagnostic and control of ruminant pestiviruses (8, 14, 15). Recent reports of genetic characterization of HoBiPev suggest that at least five subtypes (a–e) may exist (16).
Geographic Distribution of HoBiPev
Almost concurrently with the first reporting of HoBi_D32/00 in Germany, between 2003 and 2004, a HoBiPev was identified in a dairy herd in Thailand without any history of disease (17). The isolate was denominated Khonkaen, and phylogenetic analysis indicated that while it grouped with HoBi_D32/00, it was significantly divergent from the South American isolate, providing the first evidence of HoBiPev subtypes (14). The marked genetic differences between the first two isolates of HoBiPev gave a strong indication that the virus was present and evolving independently in both continents for a period of time before its identification. Following the first description and tracking of HoBiPev to an FBS that originated in Brazil, the suggestion of a novel pestivirus species circulating in South America sparked curiosity among researchers in that region, and quickly, additional cases of HoBiPev were reported, including cases previously misclassified as BVDV (3, 18–21). Currently, it has been demonstrated that HoBiPev is present in major beef- and dairy-producing areas in Brazil (south and central regions), although its true prevalence is unknown (18, 19, 22). Interestingly, in the north-eastern part of the country, HoBiPev is the most prevalent ruminant pestivirus (23). Notably, all 17 pestivirus-positive samples identified by testing 16,621 bovine serum samples belonged to the HoBiPev group (23). Interestingly, the study also tested 2,672 serum samples from small ruminants in the same region with no HoBiPev being identified (23).
In 2010, the virus was identified in Italy (8, 24). The identification of HoBiPev in Europe was a significant event, and it was theorized that additional cases would continue to arise in Europe. However, the outbreak was restricted to a single farm. Notably, after 3 years, the virus re-emerged in the same farm causing abortions (25). The origin of the virus related to the outbreak in Europe was never fully understood. However, the isolates' genetic characterization demonstrated a closer relationship to South American isolates than the Thai isolate. Analyses of archival samples from Italian herds dating back to 2005 revealed the circulation of HoBiPev in the country as early as 2007, mostly associated with samples of cattle with respiratory disease (26). Additionally, in 2019, HoBiPev was reported in Turkey in a blood sample collected between 2016 and 2017 that had previously been identified as BVDV positive. Genetic characterization classified the sequence within the HoBiPev group (27).
HoBiPev has been described in countries in the Indian subcontinent, particularly in India and Bangladesh (9, 10, 16). Those studies revealed significant genetic diversity in the isolates from that region, suggesting circulation and evolution of HoBiPev in ruminants for a prolonged time rather than a recent introduction event (9, 10). The description of the pestivirus surveillance in India suggested that HoBiPev was the most prevalent ruminant pestivirus in the studied regions based on the test of 1,049 bovine serum samples. Remarkably, out of the 20 samples positive for pestivirus, 19 were phylogenetically grouped with HoBiPev strains (10).
HoBiPev has been detected in goats in China, although without a clear association with disease (7). Recently, in 2017, an outbreak of HoBiPev with high mortality rates in beef cattle around 7–8 months old was described in China (28). The affected herd was composed of 140 animals, and the mortality rate was over 50% (78 animals). Despite unique amino acid changes identified in the E2 and Npro region of the Chinese HoBiPev-a, the possible correlation with virulence is unknown (28). The description of HoBiPev involved in severe disease cases remains a matter of concern. Further investigation is required to address whether this isolate presents an increased virulence phenotype or whether the severe clinical presentation was a consequence of multi-factorial conditions.
In addition to identifying naturally infected ruminants with HoBiPev in Brazil and European and Asian countries, there is serological evidence of HoBiPev circulation in water buffalos in Argentina (6). HoBiPev was also detected in North American, Argentinian, and Australian lots of commercial FBS (29, 30). Despite the report of contaminated FBS in lots labeled as originated from Mexico and the USA, there was no evidence for the circulation of HoBiPev during comprehensive surveillance of about 2,000 bovine serum samples representing all the mainland US states (31). Additionally, the testing of FBS lots originated and packed in the US producing plants supported that the US remained free of HoBiPev (32). Similarly, extensive characterization of pestiviruses in Mexico failed to identify HoBiPev (33, 34).
HoBiPev Infection—Clinical Remarks
Under natural or experimental conditions, calves infected with HoBiPev strains typically display mild (if any) upper respiratory signs (10, 17, 35–37). Despite the relatively low pathogenicity of HoBiPev strains identified to date, calves experimentally infected with HoBiPev strains exhibited a significant level of thymus atrophy, similar to those identified in typical virulent BVDV strains (38, 39).
More prominent disease cases involving HoBiPev were reported in Italy and China, including severe respiratory signs and diarrhea (7, 8). The high level of genome homology of the viruses isolated from those animals undergoing severe disease compared to other isolates from South America may suggest that disease severity was a consequence of different factors, including stressful conditions, other pathogens, and herd genetics. However, the emergence of highly virulent ruminant pestiviruses is a well-known phenomenon (40, 41) and eventually may occur with HoBiPev.
A key ruminant pestivirus characteristic is its tropism for fetal tissues and the establishment of persistent infection (42). Such persistently infected (PI) animals shed the virus to the environment continuously throughout their lifetimes (42, 43). We previously demonstrated that both South American and Italian non-cytopathic HoBiPev strains infected the fetus in 100% of inoculated heifers (44). The presence of HoBiPev PI animals has been reported in the field (16, 20, 22, 45). Like BVDV PIs, HoBiPev PIs also may present with the highly lethal mucosal disease (MD) syndrome (16, 20, 22, 45, 46). The MD syndrome is characterized by necrotic and erosive lesions on the gastrointestinal tract mucosa, associated with other symptoms, including enteric and respiratory signs (47). Four cases of HoBiPev-infected animals displaying MD-like symptoms have been reported (16, 20, 22, 45). All of the reports to date describe the presence of classical pathological findings comparable to BVDV MD cases. Two of these reports were from cases in Brazil. One in the north-eastern part of the country is described in a calf (20), whereas the second is an outbreak of MD-like symptoms in a case reported in the country's central west region (22).
Control and Diagnostic
Specific control measures for HoBiPev, including commercial vaccines, are unavailable. Due to the antigenic similarities that HoBiPev shares with BVDV1 and BVDV2, a study evaluating the potential cross-protection was conducted. Virus neutralization assays with HoBiPev-a, BVDV1-b, BVDV2-a, and border disease virus were performed using the serum of cattle immunized by either a MLV or killed vaccine containing both BVDV species (48). It was found that BVDV-vaccinated cattle had low cross-neutralizing antibody levels against HoBiPev-a with more than 90% of the animals demonstrating antibody-neutralizing titers to HoBiPev lower than 20 (44).
Subsequently, we demonstrated limited fetal protection to HoBiPev in cows that generated either a BVDV1 or BVDV2 PI in a previous gestation (49). HoBiPev was identified in the fetuses of 90% of infected cows, despite the cow's high level of neutralizing antibodies against BVDV1 or BVDV2 (49). Both of the studies, in vitro and in vivo, clearly demonstrated that robust immunity to either BVDV1 or 2 would have limited effect controlling the spread of HoBiPev in the event of introduction into a naïve population.
The antigenic variability among isolates belonging to the same pestivirus subtypes is described (50). Not surprisingly, the characterization of HoBiPev-a isolates in Brazil revealed significant antigenic diversity in the E2 protein, which hosts the major epitopes targeted by neutralizing antibodies (13, 19). The study conducted using eight HoBiPev-a isolates revealed that despite the conserved 5-UTR regions and clustering close together in the HoBiPev-a branch, the strains demonstrated significant antigenic diversity assessed by monoclonal antibody (MAb) panel and the level of neutralizing antibodies (19). Using 27 MAbs produced for BVDV, the reactivity of HoBiPev isolates ranged from 5 to 13 MAbs. As expected, it was verified by variation in the neutralization level of the antiserum among the different HoBiPev subtypes. There were higher cross neutralizing levels among HoBiPev-a isolates compared to both BVDV1 and 2 strains with the exception of one HoBiPev-a strain used in the study. The antiserum raised against seven HoBiPev strains had a limited neutralizing effect on the HoBiPev-a strain SV478/07, with a neutralizing level comparable or lower to the BVDV2 neutralizing level (19). The opposite was also true, the ability for the antiserum raised against SV478/07 had a limited neutralization effect on the other seven HoBiPev-a strains (19).
Based on the lack of specific control measures to HoBiPev, diagnostic testing is critical to avoid introduction of HoBiPev or its subtypes into free regions. The ability to quickly identify HoBiPev may also have a critical role in curbing viral spread. Despite its importance, specific commercial testing for HoBiPev is not available. The commercial RT-qPCR tests virotype BVDV RT-PCR Kit (Qiagen, Labor Diagnostik Leipzig GmbH, Leipzig, Germany) and VetMAX-Gold bovine virus diarrhea RNA test kit (Applied Biosystems, Life Technologies, Austin, TX, USA), designed for BVDV, demonstrated suitability in detecting positive samples from experimentally generated HoBiPev PI calves (44). The calves were harboring either the HoBi D32/00 or an Italian isolate, belonging to the subtype HoBiPev-a. Both tests accurately detected all PI animals using serum or buffy coat samples collected at day of birth (44). However, during the study, the virotype assay detected all tested samples, whereas VetMAX correctly identified about 85% of the positive samples (44). In a follow-up study conducted in India, expanding the understanding of these commercial BVDV kits in detecting divergent HoBiPev subtypes, samples spiked with the Asian HoBiPev types c and d were tested (51). The study demonstrated that virotype had higher sensitivity in detecting dilutions of these divergent subtypes than VetMAX-Gold. The virotype detection limits for HoBiPev-c and -d were 100.6 TCID50/ml and 100.3 TCID50/ml, while for VetMAX-Gold were 100.6 TCID50/ml and 102.3 TCID50/ml. However, virotype sensitivity to HoBiPev-c and -d was decreased compared to HoBiPev-a detection level (51).
Not surprisingly, the increased genetic variability of Asian HoBiPev led to increased antigenic diversity. The commercial ELISA test (IDEXX BVDV Ag/Serum Plus, IDEXX, Westbrook, ME, USA), which is based on detecting the Erns protein, mostly excels in detecting samples with HoBiPev-a (44). Although there is evidence that some HoBiPev-a strains may not be detected by this kit (15). The same kit had limited success in detecting samples with HoBiPev-c and -d, with detection limits of 104.6 TCID50/ml and 106.3 TCID50/ml (51). Other ELISA kits based on the NS3 protein typically demonstrated low sensitivity to HoBiPev-a, and the kit INgezim BVD DAS (Ingenasa, Madrid, Spain) completely failed in detecting the divergent subtypes c and d (13, 51).
Discussion
Currently, there is no nationwide eradication program for BVDV in South America, and the BVDV control is entirely voluntary at the farm or regional level. In addition, vaccination use may be restricted due to its costs, and testing may be limited to commercial ELISA kits that do not identify the specific pestivirus strain. All these factors hamper a comprehensive understanding of the true epidemiology of ruminant pestiviruses in the region. Despite these challenges, many countries in South America have reported BVDV types 1 and 2 and multiple subtypes within those viruses (18, 52–59). Other than Brazil, Argentina is the only South American country that has documented the presence of HoBiPev. The testing of fetal bovine serum lots from Argentina identified HoBiPev-a in four lots (30). Also, in Argentina, HoBiPev circulation was evidenced by the serum conversion of water buffalos to HoBiPev (6).
Considering that Brazil borders 10 countries or territories in South America, it is likely that either HoBiPev has disseminated to additional regions or there is an imminent risk of its spread. Despite the high prevalence of HoBiPev in cattle herds in Brazil, with strong evidence for it being the most prevalent ruminant pestivirus in at least the north-eastern region, the description of infection in other species in South America is restricted to water buffalos (12). Despite the testing of thousands of small ruminant samples (sheep and goats) from north-eastern Brazil, no positive sample was identified and no other report of HoBiPev in small ruminants in South America is available to date. However, it should be noted that there is a lack of systematic testing of small ruminants, so that failure to detect may be associated with failure to test. The strain identified in small ruminants in China is genetically divergent from typical HoBiPev-a, and specific mutations may have led to the increased tropism to small ruminants. Further studies are required to identify the susceptibility of ruminant species to the different HoBiPev subtypes.
Independently of the HoBiPev subtype, most acute infections are clinically indistinguishable from typical, uncomplicated BVDV1 and BVDV2 infections. The descriptions of MD-like disease associated with HoBiPev infections in different parts of the world suggest that highly fatal forms of HoBiPev infection do exist. Typically, most of the PI animals die at an early age, usually within the first 6 months of life (42). The description of MD in South American and Italy, all involving HoBiPev-a, follows the scenario observed with BVDV mucosal disease, with the description of clinical signs in calves (20, 22, 45). However, the recent description of MD-like cases in India diverges from this typical scenario (16). Nine cases resembling MD were received in a veterinary hospital between 2018 and 2019 (16). Most of the animals with MD-like symptoms were between 2 and 4 years old. In addition to the unusual animal age for the development of MD, phylogenetic analyses demonstrated that one animal was harboring HoBiPev-d, whereas the remaining eight animals were harboring a putative new HoBiPev-e (16). It remains unclear if the atypical characteristics of these cases in India correlate to the divergent HoBiPev-d and -e subtypes circulating in the country or if it is related to the biased sampling collection method.
The genetic and antigenic diversity of pestiviruses is also a well-known nemesis of vaccine design. Whereas, the benefits of using vaccines with partial protection are debatable from the standpoint of accelerating virus divergence, it may help decrease the emergence of PI animals (60). Based on the antigenic characteristics of HoBiPev, assessed by monoclonal antibody panels, HoBiPev-a isolates demonstrated common epitopes with both BVDV1 and BVDV2 strains within the E2 protein (11, 13, 19). However, both in vivo and in vitro studies suggested low to no cross-protection. In the long-term, countries in South America or Asia using BVDV vaccines may provide a favorable scenario for HoBiPev becoming the most common ruminant pestiviruses in additional regions.
It is untested whether HoBiPev strains in BVDV vaccine formulations are required to help curb HoBiPev spread. The situation in Brazil and Argentina, where only HoBiPev-a was identified, provides a better opportunity to control these viruses with the addition of a single subtype in the vaccine compared to the other regions in the world.
Despite the critical need for specific HoBiPev diagnostic, no commercial test is available. Pestivirus-free regions and BVDV endemic regions will certainly benefit from commercially available kits with the capacity to differentiate BVDV from HoBiPev. The discovery of divergent HoBiPev subtypes also questions the efficacy of in-house tests previously designed for HoBiPev-a detection (32, 51, 61). The continuous use of BVDV tests with limited sensitivity for HoBiPev could allow a “silent” introduction and dissemination of these viruses into BVDV-free or -endemic regions. Despite the lack of differentiation of the BVDV tests, the reduced genetic variability of HoBiPev currently circulating in Brazil may allow for reliable identification of cases within the region. However, introducing foreign ruminants, biologicals, and genetic material to South America, primarily if originated in Asia, should consider the possible presence of divergent HoBiPev subtypes and the risk of introduction and spread in South American cattle herds.
Author Contributions
FB and JR conceived and wrote the article. All authors contributed to the article and approved the submitted version.
Conflict of Interest
JR was employed by the company Ridpath Consulting, LLC.
The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's Note
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References
1. ICTV. Virus Taxonomy: 2018 Release. ICTV (2018). Available online at: https://talk.ictvonline.org/taxonomy/
2. Smith DB, Meyers G, Bukh J, Gould EA, Monath T, Muerhoff AS, et al. Proposed revision to the taxonomy of the genus Pestivirus, family Flaviviridae. J Gen Virol. (2017) 8:2106–12. doi: 10.1099/jgv.0.000873
3. Bauermann FV, Ridpath JF. HoBi-like viruses - the typical “atypical bovine pestivirus.” Anim Heal Res Rev. (2015) 16:64–9. doi: 10.1017/S146625231500002X
4. Honorato Gatto IR, Sonálio K, de Oliveira LG. Atypical porcine pestivirus (APPV) as a new species of pestivirus in pig production. Front Vet Sci. (2019) 6:35. doi: 10.3389/fvets.2019.00035
5. Arruda B, Arruda P, Hensch M, Chen Q, Zheng Y, Yang C, et al. Porcine astrovirus type 3 in central nervous system of swine with polioencephalomyelitis. Emerg Infect Dis. (2017) 23:2097–100. doi: 10.3201/eid2312.170703
6. Pecora A, Pérez Aguirreburualde MS, Malacari DA, Zabal O, Sala JM, Konrad JL, et al. Serologic evidence of HoBi-like virus circulation in Argentinean water buffalo. J Vet Diagnostic Investig. (2017) 29:926–9. doi: 10.1177/1040638717720246
7. Shi H, Kan Y, Yao L, Leng C, Tang Q, Ji J, et al. Identification of natural infections in sheep/Goats with HoBi-like Pestiviruses in China. Transbound Emerg Dis. (2016) 63:480–4. doi: 10.1111/tbed.12551
8. Decaro N, Lucente MS, Mari V, Cirone F, Cordioli P, Camero M, et al. Atypical pestivirus and severe respiratory disease in calves, Europe. Emerg Infect Dis. (2011) 17:1549–52. doi: 10.3201/eid1708.101447
9. Haider N, Rahman MS, Khan SU, Mikolon A, Gurley ES, Osmani MG, et al. Identification and epidemiology of a rare hobi-like pestivirus strain in Bangladesh. Transbound Emerg Dis. (2014) 61:193–8. doi: 10.1111/tbed.12218
10. Mishra N, Rajukumar K, Pateriya A, Kumar M, Dubey P, Behera SP, et al. Identification and molecular characterization of novel and divergent HoBi-like pestiviruses from naturally infected cattle in India. Vet Microbiol. (2014) 174:239–46. doi: 10.1016/j.vetmic.2014.09.017
11. Schirrmeier H, Strebelow G, Depner K, Hoffmann B, Beer M. Genetic and antigenic characterization of an atypical pestivirus isolate, a putative member of a novel pestivirus species. J Gen Virol. (2004) 85:3647–52. doi: 10.1099/vir.0.80238-0
12. Bauermann FV, Ridpath JF, Weiblen R, Flores EF. HoBi-like viruses: an emerging group of pestiviruses. J Vet Diagnostic Investig. (2013) 25:6–15. doi: 10.1177/1040638712473103
13. Bauermann FV, Flores EF, Ridpath JF. Antigenic relationships between Bovine viral diarrhea virus 1 and 2 and HoBi virus: possible impacts on diagnosis and control. J Vet Diagnostic Investig. (2012) 24:253–61. doi: 10.1177/1040638711435144
14. Liu L, Kampa J, Belák S, Baule C. Virus recovery and full-length sequence analysis of atypical bovine pestivirus Th/04_KhonKaen. Vet Microbiol. (2009) 138:62–8. doi: 10.1016/j.vetmic.2009.03.006
15. Peletto S, Zuccon F, Pitti M, Gobbi E, Marco L De, Caramelli M, et al. Detection and phylogenetic analysis of an atypical pestivirus, strain IZSPLV_To. Res Vet Sci. (2012) 92:147–50. doi: 10.1016/j.rvsc.2010.10.015
16. Kalaiyarasu S, Mishra N, Jayalakshmi K, Selvaraj P, Sudhakar SB, Jhade SK, et al. Molecular characterization of recent HoBi-like pestivirus isolates from cattle showing mucosal disease-like signs in India reveals emergence of a novel genetic lineage. Transbound Emerg Dis. (2021). doi: 10.1111/tbed.13981
17. Ståhl K, Kampa J, Alenius S, Persson Wadman A, Baule C, Aiumlamai S, et al. Natural infection of cattle with an atypical'HoBi'-like pestivirus - implications for BVD control and for the safety of biological products. Vet Res. (2007) 38:517–23. doi: 10.1051/vetres:2007012
18. Silveira S, Weber MN, Mósena ACS, da Silva MS, Streck AF, Pescador CA, et al. Genetic diversity of brazilian bovine pestiviruses detected between 1995 and 2014. Transbound Emerg Dis. (2017) 64:613–23. doi: 10.1111/tbed.12427
19. Dias RK, Cargnelutti JF, Weber MN, Canal CW, Bauermann FV, Ridpath JF, et al. Antigenic diversity of Brazilian isolates of HoBi-like pestiviruses. Vet Microbiol. (2017) 203:221–8. doi: 10.1016/j.vetmic.2017.03.021
20. Weber MN, Mósena ACS, Simões SVD, Almeida LL, Pessoa CRM, Budaszewski RF, et al. Clinical presentation resembling mucosal disease associated with'HoBi'-like pestivirus in a field outbreak. Transbound Emerg Dis. (2016) 63:92–100. doi: 10.1111/tbed.12223
21. Cortez A, Heinemann MB, De Castro AMMG, Soares RM, Pinto AMV, Alfieri AA, et al. Genetic characterization of Brazilian bovine viral diarrhea virus isolates by partial nucleotide sequencing of the 5′-UTR region. Pesqui Vet Bras. (2006) 26:211–6. doi: 10.1590/S0100-736X2006000400005
22. Cruz RAS, Rodrigues WB, Silveira S, Oliveira VHS, Campos CG, Leite Filho RV, et al. Mucosal disease-like lesions caused by HoBi-like pestivirus in Brazilian calves in 2010–2011: clinical, pathological, immunohistochemical, and virological characterization. Res Vet Sci. (2018) 119:116–21. doi: 10.1016/j.rvsc.2018.06.010
23. Silveira S, Baumbach LF, Weber MN, Mósena ACS, da Silva MS, Cibulski SP, et al. HoBi-like is the most prevalent ruminant pestivirus in Northeastern Brazil. Transbound Emerg Dis. (2018) 65:113–20. doi: 10.1111/tbed.12689
24. Decaro N, Lucente MS, Mari V, Sciarretta R, Pinto P, Buonavoglia D, et al. Hobi-like pestivirus in aborted bovine fetuses. J Clin Microbiol. (2012) 50:509–12. doi: 10.1128/JCM.05887-11
25. Decaro N, Lucente MS, Losurdo M, Larocca V, Elia G, Occhiogrosso L, et al. HoBi-like pestivirus and its impact on cattle productivity. Transbound Emerg Dis. (2016) 63:469–73. doi: 10.1111/tbed.12529
26. Decaro N, Mari V, Lucente MS, Sciarretta R, Elia G, Ridpath JF, et al. Detection of a Hobi-like virus in archival samples suggests circulation of this emerging pestivirus species in Europe prior to 2007. Vet Microbiol. (2013) 167:307–13. doi: 10.1016/j.vetmic.2013.09.006
27. Timurkan MÖ, Aydin H. Increased genetic diversity of BVDV strains circulating in Eastern Anatolia, Turkey: first detection of BVDV-3 in Turkey. Trop Anim Health Prod. (2019) 51:1953–61. doi: 10.1007/s11250-019-01901-6
28. Chen M, Liu M, Liu S, Shang Y. HoBi-like pestivirus infection leads to bovine death and severe respiratory disease in China. Transbound Emerg Dis. (2020) 68:1069–74. doi: 10.1111/tbed.13832
29. Xia H, Vijayaraghavan B, Belák S, Liu L. Detection and identification of the atypical bovine pestiviruses in commercial foetal bovine serum batches. PLoS ONE. (2011) 6:e28553. doi: 10.1371/journal.pone.0028553
30. Pecora A, Perez Aguirreburualde MS, Ridpath JF, Dus Santos MJ. Molecular characterization of pestiviruses in fetal bovine sera originating from Argentina: evidence of circulation of HoBi-like viruses. Front Vet Sci. (2019) 6:359. doi: 10.3389/fvets.2019.00359
31. Bauermann FV, Ridpath JF, Dargatz DA. A serosurvey for ruminant pestivirus exposure conducted using cattle sera collected for brucellosis surveillance in the United States. J Vet Diagnostic Investig. (2016) 29:76–82. doi: 10.1177/1040638716680251
32. Bauermann FV, Flores EF, Falkenberg SM, Weiblen R, Ridpath JF. Lack of evidence for the presence of emerging HoBi-like viruses in North American fetal bovine serum lots. J Vet Diagnostic Investig. (2014) 26:10–7. doi: 10.1177/1040638713518208
33. Gómez-Romero N, Basurto-Alcántara FJ, Verdugo-Rodríguez A, Lagunes-Quintanilla R, Bauermann FV, Ridpath JF. Detection of border disease virus in Mexican cattle. Transbound Emerg Dis. (2017) 65:267–71. doi: 10.1111/tbed.12641
34. Gómez-Romero N, Basurto-Alcántara FJ, Verdugo-Rodríguez A, Bauermann FV, Ridpath JF. Genetic diversity of bovine viral diarrhea virus in cattle from Mexico. J Vet Diagnostic Investig. (2017) 29:362–5. doi: 10.1177/1040638717690187
35. Larska M, Polak MP, Riitho V, Strong R, Belák S, Alenius S, et al. Kinetics of single and dual infection of calves with an Asian atypical bovine pestivirus and a highly virulent strain of bovine viral diarrhoea virus 1. Comp Immunol Microbiol Infect Dis. (2012) 35:381–90. doi: 10.1016/j.cimid.2012.03.003
36. Bauermann FV, Falkenberg SM, Decaro N, Flores EF, Ridpath JF. Experimental infection of calves, sheep, goats and pigs with HoBi-like viruses by direct inoculation or exposure to persistently infected calves. Vet Microbiol. (2015) 181:289–93. doi: 10.1016/j.vetmic.2015.10.011
37. Decaro N, Mari V, Lucente MS, Sciarretta R, Moreno A, Armenise C, et al. Experimental infection of cattle, sheep and pigs with'Hobi'-like pestivirus. Vet Microbiol. (2012) 155:165–71. doi: 10.1016/j.vetmic.2011.08.030
38. Falkenberg SM, Johnson C, Bauermann FV, McGill J, Palmer MV, Sacco RE, et al. Changes observed in the thymus and lymph nodes 14 days after exposure to BVDV field strains of enhanced or typical virulence in neonatal calves. Vet Immunol Immunopathol. (2014) 160:70–80. doi: 10.1016/j.vetimm.2014.03.018
39. Falkenberg SM, Bauermann FV, Ridpath JF. Characterization of thymus-associated lymphoid depletion in bovine calves acutely or persistently infected with bovine viral diarrhea virus 1, bovine viral diarrhea virus 2 or HoBi-like pestivirus. Arch Virol. (2017) 162:3473–80. doi: 10.1007/s00705-017-3523-x
40. Gethmann J, Homeier T, Holsteg M, Schirrmeier H, Saßerath M, Hoffmann B, et al. BVD-2 outbreak leads to high losses in cattle farms in Western Germany. Heliyon. (2015) 1:e00019. doi: 10.1016/j.heliyon.2015.e00019
41. Liebler-Tenorio EM, Ridpath JF, Neill JD. Lesions and tissue distribution of viral antigen in severe acute versus subclinical acute infection with BVDV2. Biologicals. (2003) 31:119–22. doi: 10.1016/S1045-1056(03)00026-5
43. Houe H. Epidemiological features and economical importance of bovine virus diarrhoea virus (BVDV) infections. Vet Microbiol. (1999) 64:89–107. doi: 10.1016/S0378-1135(98)00262-4
44. Bauermann FV, Falkenberg SM, Vander Ley B, Decaro N, Brodersen BW, Harmon A, et al. Generation of calves persistently infected with HoBi-like pestivirus and comparison of methods for detection of these persistent infections. J Clin Microbiol. (2014) 52:3845–52. doi: 10.1128/JCM.01563-14
45. Decaro N, Lanave G, Lucente MS, Mari V, Varello K, Losurdo M, et al. Mucosal disease-like syndrome in a calf persistently infected by Hobi-like pestivirus. J Clin Microbiol. (2014) 52:2946–54. doi: 10.1128/JCM.00986-14
46. Deregt D, Loewen KG. Bovine viral diarrhea virus: biotypes and disease. Can Vet J. (1995) 36:371–8.
47. Tautz N, Meyers G, Thiel HJ. Pathogenesis of mucosal disease, a deadly disease of cattle caused by a pestivirus. Clin Diagnostic Virol. (1998) 10:121–7. doi: 10.1016/S0928-0197(98)00037-3
48. Bauermann FV, Harmon A, Flores EF, Falkenberg SM, Reecy JM, Ridpath JF. In vitro neutralization of HoBi-like viruses by antibodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea viruses 1 and 2. Vet Microbiol. (2013) 166:242–5. doi: 10.1016/j.vetmic.2013.04.032
49. Bauermann FV, Falkenberg SM, Ridpath JF. HoBi-like virus RNA detected in foetuses following challenge of pregnant cows that had previously given birth to calves persistently infected with Bovine Viral Diarrhoea virus. Transbound Emerg Dis. (2016) 64:1624–32. doi: 10.1111/tbed.12556
50. Fulton RW, Ridpath JF, Confer AW, Saliki JT, Burge LJ, Payton ME. Bovine viral diarrhoea virus antigenic diversity: impact on disease and vaccination programmes. Biologicals. (2003) 31:89–95. doi: 10.1016/S1045-1056(03)00021-6
51. Moorthy D, Mishra N, Kalaiyarasu S, Jhade SK, Singh VP. Evaluation of currently available bovine viral diarrhoea virus (BVDV) and HoBi-like pestivirus (HoBiPeV) specific diagnostic tests in detection of highly divergent HoBiPeVs in cattle. J Virol Methods. (2019) 272:113707. doi: 10.1016/j.jviromet.2019.113707
52. Donoso A, Inostroza F, Celedón M, Pizarro-Lucero J. Genetic diversity of Bovine viral diarrhea virus from cattle in Chile between 2003 and 2007. BMC Vet Res. (2018) 14:314. doi: 10.1186/s12917-018-1641-7
53. Ståhl K, Benito A, Felmer R, Zuñiga J, Reinhardt G, Rivera H, et al. Genetic diversity of bovine viral diarrhoea virus (BVDV) from Peru and Chile. Pesqui Vet Bras. (2009) 29:41–4. doi: 10.1590/S0100-736X2009000100006
54. Ortega DO, Sarmiento RAM, Torreglosa JCT, Rocha JF. Prevalence and risk factors of bovine viral diarrhea in Colombian cattle. Vet World. (2020) 13:1487–94. doi: 10.14202/vetworld.2020.1487-1494
55. Obando C, Baule C, Pedrique C, Veracierta C, Belák S, Merza M, et al. Serological and molecular diagnosis of Bovine viral diarrhoea virus and evidence of other viral infections in dairy calves with respiratory disease in venezuela. Acta Vet Scand. (1999) 40:253–62. doi: 10.1186/BF03547023
56. Saa LR, Perea A, García-Bocanegra I, Arenas AJ, Jara DV, Ramos R, et al. Seroprevalence and risk factors associated with bovine viral diarrhea virus (BVDV) infection in non-vaccinated dairy and dual purpose cattle herds in Ecuador. Trop Anim Health Prod. (2012) 44:645–9. doi: 10.1007/s11250-011-9948-4
57. Pecora A, Malacari DA, Ridpath JF, Perez Aguirreburualde MS, Combessies G, Odeón AC, et al. First finding of genetic and antigenic diversity in 1b-BVDV isolates from Argentina. Res Vet Sci. (2014) 96:204–12. doi: 10.1016/j.rvsc.2013.11.004
58. Maya L, Puentes R, Reolón E, Acuña P, Riet F, Rivero R, et al. Molecular diversity of bovine viral diarrhea virus in Uruguay. Arch Virol. (2016) 161:529–35. doi: 10.1007/s00705-015-2688-4
59. Flores EF, Cargnelutti JF, Monteiro FL, Bauermann FV, Ridpath JF, Weiblen R. A genetic profile of bovine pestiviruses circulating in Brazil (1998-2018). Anim Heal Res Rev. (2019) 19:134–41. doi: 10.1017/S1466252318000130
60. Newcomer BW, Chamorro MF, Walz PH. Vaccination of cattle against bovine viral diarrhea virus. Vet Microbiol. (2017) 206:78–83. doi: 10.1016/j.vetmic.2017.04.003
Keywords: atypical bovine pestivirus, control, diagnostic, HoBi-like virus, South America
Citation: Bauermann FV and Ridpath JF (2021) Epidemiology of Pestivirus H in Brazil and Its Control Implications. Front. Vet. Sci. 8:693041. doi: 10.3389/fvets.2021.693041
Received: 09 April 2021; Accepted: 11 June 2021;
Published: 23 July 2021.
Edited by:
Marta Hernandez-Jover, Charles Sturt University, AustraliaReviewed by:
Juan Manuel Sanhueza, Catholic University of Temuco, ChileBibiana Benavides, University of Nariño, Colombia
Copyright © 2021 Bauermann and Ridpath. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Fernando V. Bauermann, fernando.vicosa_bauermann@okstate.edu