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Paul Becher - One of the best experts on this subject based on the ideXlab platform.
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Genetically distinct Pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept.
Emerging microbes & infections, 2020Co-Authors: Alexander Postel, Paul BecherAbstract:Classical swine fever (CSF) is one of the most important viral diseases of pigs. In many countries, the use of vaccines is restricted due to limitations of subunit vaccines with regard to efficacy and onset of protection as well as failure of live vaccines to differentiate infected from vaccinated animals (DIVA principle). Chimeric Pestiviruses based on CSF virus (CSFV) and the related bovine viral diarrhea virus (BVDV) have been licensed as live marker vaccines in Europe and Asia, but cross-reactive antibodies can cause problems in DIVA application due to close antigenic relationship. To develop marker vaccine candidates with improved DIVA properties, three chimeric viruses were generated by replacing Erns of CSFV Alfort-Tubingen with homologue proteins of only distantly related Pestiviruses. The chimeric viruses "Ra", "Pro", and "RaPro" contained Erns sequences of Norway rat and Pronghorn Pestiviruses or a combination of both, respectively. In porcine cells, the "Pro" chimera replicated to high titers, while replication of the "Ra" chimera was limited. The "RaPro" chimera showed an intermediate phenotype. All vaccine candidates were attenuated in a vaccination/ challenge trial in pigs, but to different extents. Inoculation induced moderate to high levels of neutralizing antibodies that protected against infection with a genetically heterologous, highly virulent CSFV. Importantly, serum samples of vaccinated animals did not show any cross-reactivity in a CSFV Erns antibody ELISA. In conclusion, the Erns antigen from distantly related Pestiviruses can provide a robust serological negative marker for a new generation of improved CSFV marker vaccines based on the chimeric pestivirus concept.
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CRISPR/Cas9-Mediated Knockout of DNAJC14 Verifies This Chaperone as a Pivotal Host Factor for RNA Replication of Pestiviruses.
Journal of virology, 2019Co-Authors: Olaf Isken, Paul Becher, Alexander Postel, B Bruhn, E. Lattwein, Norbert TautzAbstract:Pestiviruses like bovine viral diarrhea virus (BVDV) are a threat to livestock. For Pestiviruses, cytopathogenic (cp) and noncytopathogenic (noncp) strains are distinguished in cell culture. The noncp biotype of BVDV is capable of establishing persistent infections, which is a major problem in disease control. The noncp biotype rests on temporal control of viral RNA replication, mediated by regulated cleavage of nonstructural protein 2-3 (NS2-3). This cleavage is catalyzed by the autoprotease in NS2, the activity of which depends on its cellular cofactor, DNAJC14. Since this chaperone is available in small amounts and binds tightly to NS2, NS2-3 translated later in infection is no longer cleaved. As NS3 is an essential constituent of the viral replicase, this shift in polyprotein processing correlates with downregulation of RNA replication. In contrast, cp BVDV strains arising mostly by RNA recombination show highly variable genome structures and display unrestricted NS3 release. The functional importance of DNAJC14 for noncp Pestiviruses has been established so far only for BVDV-1. It was therefore enigmatic whether replication of other noncp Pestiviruses is also DNAJC14 dependent. By generating bovine and porcine DNAJC14 knockout cells, we could show that (i) replication of 6 distinct noncp pestivirus species (A to D, F, and G) depends on DNAJC14, (ii) the pestiviral replicase NS3-5B can assemble into functional complexes in the absence of DNAJC14, and (iii) all cp Pestiviruses replicate their RNA and generate infectious progeny independent of host DNAJC14. Together, these findings confirm DNAJC14 as a pivotal cellular cofactor for the replication and maintenance of the noncp biotype of Pestiviruses.IMPORTANCE Only noncp pestivirus strains are capable of establishing life-long persistent infections to generate the virus reservoir in the field. The molecular basis for this biotype is only partially understood and only investigated in depth for BVDV-1 strains. Temporal control of viral RNA replication correlates with the noncp biotype and is mediated by limiting amounts of cellular DNAJC14 that activate the viral NS2 protease to catalyze the release of the essential replicase component NS3. Here, we demonstrate that several species of noncp Pestiviruses depend on DNAJC14 for their RNA replication. Moreover, all cp Pestiviruses, in sharp contrast to their noncp counterparts, replicate independently of DNAJC14. The generation of a cp BVDV in the persistently infected animal is causative for onset of mucosal disease. Therefore, the observed strict biotype-specific difference in DNAJC14 dependency should be further examined for its role in cell type/tissue tropism and the pathogenesis of this lethal disease.
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crispr cas9 mediated knockout of dnajc14 verifies this chaperone as a pivotal host factor for rna replication of Pestiviruses
Journal of Virology, 2018Co-Authors: Olaf Isken, Paul Becher, Alexander Postel, B Bruhn, E. Lattwein, Norbert TautzAbstract:Pestiviruses like bovine viral diarrhea virus (BVDV) are a threat to livestock. For Pestiviruses, cytopathogenic (cp) and noncytopathogenic (noncp) strains are distinguished in cell culture. The noncp biotype of BVDV is capable of establishing persistent infections, which is a major problem in disease control. The noncp biotype rests on temporal control of viral RNA replication, mediated by regulated cleavage of nonstructural protein 2-3 (NS2-3). This cleavage is catalyzed by the autoprotease in NS2, the activity of which depends on its cellular cofactor, DNAJC14. Since this chaperone is available in small amounts and binds tightly to NS2, NS2-3 translated later in infection is no longer cleaved. As NS3 is an essential constituent of the viral replicase, this shift in polyprotein processing correlates with downregulation of RNA replication. In contrast, cp BVDV strains arising mostly by RNA recombination show highly variable genome structures and display unrestricted NS3 release. The functional importance of DNAJC14 for noncp Pestiviruses has been established so far only for BVDV-1. It was therefore enigmatic whether replication of other noncp Pestiviruses is also DNAJC14 dependent. By generating bovine and porcine DNAJC14 knockout cells, we could show that (i) replication of 6 distinct noncp pestivirus species (A to D, F, and G) depends on DNAJC14, (ii) the pestiviral replicase NS3-5B can assemble into functional complexes in the absence of DNAJC14, and (iii) all cp Pestiviruses replicate their RNA and generate infectious progeny independent of host DNAJC14. Together, these findings confirm DNAJC14 as a pivotal cellular cofactor for the replication and maintenance of the noncp biotype of Pestiviruses.IMPORTANCE Only noncp pestivirus strains are capable of establishing life-long persistent infections to generate the virus reservoir in the field. The molecular basis for this biotype is only partially understood and only investigated in depth for BVDV-1 strains. Temporal control of viral RNA replication correlates with the noncp biotype and is mediated by limiting amounts of cellular DNAJC14 that activate the viral NS2 protease to catalyze the release of the essential replicase component NS3. Here, we demonstrate that several species of noncp Pestiviruses depend on DNAJC14 for their RNA replication. Moreover, all cp Pestiviruses, in sharp contrast to their noncp counterparts, replicate independently of DNAJC14. The generation of a cp BVDV in the persistently infected animal is causative for onset of mucosal disease. Therefore, the observed strict biotype-specific difference in DNAJC14 dependency should be further examined for its role in cell type/tissue tropism and the pathogenesis of this lethal disease.
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Close Relationship of Ruminant Pestiviruses and Classical Swine Fever Virus
Emerging infectious diseases, 2015Co-Authors: Alexander Postel, Tuba Cigdem Oguzoglu, Stefanie Schmeiser, Daniela Indenbirken, Malik Alawi, Nicole Fischer, Adam Grundhoff, Paul BecherAbstract:Pestiviruses are enveloped viruses within the family Flaviviridae that have a highly variable single-stranded positive-sense RNA genome of ≈12.3 kb (1). The genus Pestivirus comprises the established species bovine viral diarrhea virus (BVDV)–1, BVDV-2, border disease virus (BDV), and classical swine fever virus (CSFV), as well as a growing number of additional tentative Pestivirus species. CSFV is the causative agent for classical swine fever, which is notifiable to the World Organisation of Animal Health because it is highly contagious and can cause great loss of pigs (2–4). For a given country, CSFV-positive status severely diminishes international trade of pigs and pig products. Accordingly, because of cross-reacting antibodies, infections of pigs (nonruminants) with ruminant Pestiviruses, which occasionally occur under natural conditions, can cause serious problems with regard to serologic diagnosis of classical swine fever (5). In Turkey, 2 Pestiviruses, Aydin/04 and Burdur/05, have been isolated from a sheep and a goat with clinical signs of border disease (6). A detailed genetic and antigenic characterization revealed that these 2 isolates must be regarded as representatives of a new Pestivirus species that is closely related to CSFV and can cause serious diagnostic problems in established CSFV serology.
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Heterogeneity of ruminant Pestiviruses: academic interest or important basis for the development of vaccines and diagnostics?
Berliner und Munchener tierarztliche Wochenschrift, 2003Co-Authors: Matthias König, Cedillo Rosales S, Paul Becher, H.-j. ThielAbstract:Pestiviruses cause economically important diseases of farm animals. Members of the Pestiviruses are bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, classical swine fever virus (CSFV) and border disease virus (BDV). Phylogenetic analyses based on the entire nucleic acid sequence encoding the Npro allow a statistically significant segregation of established species and of subgroups within the species. BVDV-1 strains isolated in Germany can be associated with at least five different subgroups. In contrast all BVDV-2 isolates detected in Germany so far are closely related, belonging to one subgroup. A group of virus isolates from sheep and zoo animals is clearly different from established pestivirus species and can be designated as BDV-2. Antigenetic relatedness of Pestiviruses was studied using defined virus isolates and antisera in cross-neutralization assays. Six antigenic groups were distinguished corresponding to the genetic clusters BVDV-1, BVDV-2, CSFV, BDV-1, BDV-2 and Giraffe-1. A significant antigenic difference was also observed between members of subgroups 1a and 1b of BVDV-1. Studies on the genetic and antigenic heterogeneity of Pestiviruses are important for the development of new vaccines, diagnostic tests and for eradication programs.
Sándor Belák - One of the best experts on this subject based on the ideXlab platform.
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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
Comparative Immunology Microbiology and Infectious Diseases, 2012Co-Authors: Magdalena Larska, Sándor Belák, Stefan Alenius, Åse Uttenthal, M P Polak, Victor Riitho, Rebecca Strong, Lihong LiuAbstract:Atypical bovine Pestiviruses related to bovine viral diarrhoea virus (BVDV) have recently been detected in cattle from South America, Asia and Europe. The purpose of this study was to compare the clinical and virological aspects of dual infection with BVDV-1 (Horton 916) and an Asian atypical bovine pestivirus (Th/04_KhonKaen) in naive calves, in comparison to single infections. Milder clinical signs were observed in the animals infected with single Th/04_KhonKaen strain. Leukocytopenia and lymphocytopenia were observed in all infected groups at a similar level which correlated with the onset of viraemia. Co-infection with both viruses led to prolonged fever in comparison to single strain inoculated groups and simultaneous replication of concurrent viruses in blood and in the upper respiratory tract. Following the infections all the calves seroconverted against homologous strains. Atypical Pestiviruses pose a serious threat to livestock health and BVDV eradication, since they may have the potential to be widely spread in cattle populations without being detected and differentiated from other BVDV infections.
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Atypical Pestivirus and Severe Respiratory Disease in Calves, Europe
Emerging infectious diseases, 2012Co-Authors: Lihong Liu, Karl Ståhl, Stefan Alenius, Hongyan Xia, Magdalena Larska, Åse Uttenthal, Mirosław P. Polak, Hu Shan, Hong Yin, Sándor BelákAbstract:To the Editor: The article by Decaro et al. (1) described an outbreak of severe respiratory disease in calves in Italy caused by an atypical bovine pestivirus. This report confirms our concern that this group of viruses is probably widespread (2) and present on >3 continents. Moreover, it demonstrates that atypical bovine Pestiviruses are capable of causing disease in calves in the field and a clinical picture consistent with most bovine viral diarrhea virus (BVDV) infections that occur naturally or experimentally (3,4). Some key issues remain unknown. The origin of the bovine pestivirus and the route of introduction into the herd are unclear, although phylogenies demonstrated a close relationship between this virus strain from Italy and atypical bovine Pestiviruses from Brazil. Batches of fetal bovine serum from Brazil have repeatedly been found to be contaminated with atypical bovine Pestiviruses (2,3), and there is a risk for contamination of vaccines with these viruses. Animal trade and vaccines should be considered when conducting further investigations into this outbreak. The evolutionary relationship between the atypical and the recognized pestivirus species (1) needs to be clarified. Maximum-likelihood and Bayesian analyses of a concatenated dataset positioned atypical Pestiviruses consistently in a clade sister to BVDV-1 and BVDV-2, and the larger clade was sister to pestivirus of giraffes (5). The same pattern was observed in complete genome phylogeny (1). The term atypical is not informative, and a new name has been proposed for these bovine Pestiviruses (5). Outcomes of infections with these viruses are typical, but the viral antigens and phylogenies are unique.
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Detection and Identification of the Atypical Bovine Pestiviruses in Commercial Foetal Bovine Serum Batches
PloS one, 2011Co-Authors: Hongyan Xia, Sándor Belák, Balaje Vijayaraghavan, Lihong LiuAbstract:The recently emerging atypical bovine Pestiviruses have been detected in commercial foetal bovine serum (FBS) of mainly South American origin so far. It is unclear how widely the viruses are presented in commercial FBS of different geographic origins. To further investigate the possible pestivirus contamination of commercially available FBS batches, 33 batches of FBS were obtained from ten suppliers and analysed in this study for the presence of both the recognised and the atypical bovine Pestiviruses. All 33 batches of FBS were positive by real-time RT-PCR assays for at least one species of bovine Pestiviruses. According to the certificate of analysis that the suppliers claimed for each batch of FBS, BVDV-1 was detected in all 11 countries and BVDV-2 was detected exclusively in the America Continent. The atypical Pestiviruses were detected in 13 batches claimed to originate from five countries. Analysis of partial 5'UTR sequences showed a high similarity among these atypical bovine Pestiviruses. This study has demonstrated, for the first time that commercial FBS batches of different geographic origins are contaminated not only with the recognised species BVDV-1 and BVDV-2, but also with the emerging atypical bovine Pestiviruses.
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Effects of methodology and analysis strategy on robustness of pestivirus phylogeny
Virus Research, 2009Co-Authors: Claudia Baule, Sándor Belák, Niklas WahlbergAbstract:Abstract Phylogenetic analysis of Pestiviruses is a useful tool for classifying novel Pestiviruses and for revealing their phylogenetic relationships. In this study, robustness of pestivirus phylogenies has been compared by analyses of the 5′UTR, and complete N pro and E2 gene regions separately and combined, performed by four methods: neighbour-joining (NJ), maximum parsimony (MP), maximum likelihood (ML), and Bayesian inference (BI). The strategy of analysing the combined sequence dataset by BI, ML, and MP methods resulted in a single, well-supported tree topology, indicating a reliable and robust pestivirus phylogeny. By contrast, the single-gene analysis strategy resulted in 12 trees of different topologies, revealing different relationships among Pestiviruses. These results indicate that the strategies and methodologies are two vital aspects affecting the robustness of the pestivirus phylogeny. The strategy and methodologies outlined in this paper may have a broader application in inferring phylogeny of other RNA viruses.
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virus recovery and full length sequence analysis of atypical bovine pestivirus th 04_khonkaen
Veterinary Microbiology, 2009Co-Authors: Lihong Liu, Sándor Belák, Jaruwan Kampa, Claudia BauleAbstract:Phylogenetic analysis of recently identified “atypical” bovine Pestiviruses, performed based on different gene regions, has revealed unclear relationships with other established species, therefore, their phylogenetic position could not be determined so far. In this study, the atypical pestivirus Th/04_KhonKaen was recovered from serum of a naturally infected calf and the complete genome sequence was determined and analysed, as means to define its position. The viral genome is 12,337 nucleotides (nt) long, and comprises a 5′-UTR of 383 nt, a 3′-UTR of 254 nt and an open reading frame of 11,700 nt, without duplication of viral sequences or insertions of cellular sequences. The phylogenetic analyses of the full-length sequence, performed by Neighbor-joining, Maximum likelihood, and the Bayesian approach, unanimously placed Th/04_KhonKaen in a single lineage, distinct from the established pestivirus species, and close to bovine viral diarrhea virus types 1 and 2. Furthermore, Th/04_KhonKaen and two previously reported atypical Pestiviruses D32/00_‘HoBi’ and CH-KaHo/cont formed a well-supported monophyletic clade in trees based on the complete Npro and E2 gene regions. The finding provides conclusive classification of the Th/04_KhonKaen virus and confirms the standing of the “atypical” bovine Pestiviruses as a novel pestivirus species.
Lihong Liu - One of the best experts on this subject based on the ideXlab platform.
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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
Comparative Immunology Microbiology and Infectious Diseases, 2012Co-Authors: Magdalena Larska, Sándor Belák, Stefan Alenius, Åse Uttenthal, M P Polak, Victor Riitho, Rebecca Strong, Lihong LiuAbstract:Atypical bovine Pestiviruses related to bovine viral diarrhoea virus (BVDV) have recently been detected in cattle from South America, Asia and Europe. The purpose of this study was to compare the clinical and virological aspects of dual infection with BVDV-1 (Horton 916) and an Asian atypical bovine pestivirus (Th/04_KhonKaen) in naive calves, in comparison to single infections. Milder clinical signs were observed in the animals infected with single Th/04_KhonKaen strain. Leukocytopenia and lymphocytopenia were observed in all infected groups at a similar level which correlated with the onset of viraemia. Co-infection with both viruses led to prolonged fever in comparison to single strain inoculated groups and simultaneous replication of concurrent viruses in blood and in the upper respiratory tract. Following the infections all the calves seroconverted against homologous strains. Atypical Pestiviruses pose a serious threat to livestock health and BVDV eradication, since they may have the potential to be widely spread in cattle populations without being detected and differentiated from other BVDV infections.
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Atypical Pestivirus and Severe Respiratory Disease in Calves, Europe
Emerging infectious diseases, 2012Co-Authors: Lihong Liu, Karl Ståhl, Stefan Alenius, Hongyan Xia, Magdalena Larska, Åse Uttenthal, Mirosław P. Polak, Hu Shan, Hong Yin, Sándor BelákAbstract:To the Editor: The article by Decaro et al. (1) described an outbreak of severe respiratory disease in calves in Italy caused by an atypical bovine pestivirus. This report confirms our concern that this group of viruses is probably widespread (2) and present on >3 continents. Moreover, it demonstrates that atypical bovine Pestiviruses are capable of causing disease in calves in the field and a clinical picture consistent with most bovine viral diarrhea virus (BVDV) infections that occur naturally or experimentally (3,4). Some key issues remain unknown. The origin of the bovine pestivirus and the route of introduction into the herd are unclear, although phylogenies demonstrated a close relationship between this virus strain from Italy and atypical bovine Pestiviruses from Brazil. Batches of fetal bovine serum from Brazil have repeatedly been found to be contaminated with atypical bovine Pestiviruses (2,3), and there is a risk for contamination of vaccines with these viruses. Animal trade and vaccines should be considered when conducting further investigations into this outbreak. The evolutionary relationship between the atypical and the recognized pestivirus species (1) needs to be clarified. Maximum-likelihood and Bayesian analyses of a concatenated dataset positioned atypical Pestiviruses consistently in a clade sister to BVDV-1 and BVDV-2, and the larger clade was sister to pestivirus of giraffes (5). The same pattern was observed in complete genome phylogeny (1). The term atypical is not informative, and a new name has been proposed for these bovine Pestiviruses (5). Outcomes of infections with these viruses are typical, but the viral antigens and phylogenies are unique.
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Detection and Identification of the Atypical Bovine Pestiviruses in Commercial Foetal Bovine Serum Batches
PloS one, 2011Co-Authors: Hongyan Xia, Sándor Belák, Balaje Vijayaraghavan, Lihong LiuAbstract:The recently emerging atypical bovine Pestiviruses have been detected in commercial foetal bovine serum (FBS) of mainly South American origin so far. It is unclear how widely the viruses are presented in commercial FBS of different geographic origins. To further investigate the possible pestivirus contamination of commercially available FBS batches, 33 batches of FBS were obtained from ten suppliers and analysed in this study for the presence of both the recognised and the atypical bovine Pestiviruses. All 33 batches of FBS were positive by real-time RT-PCR assays for at least one species of bovine Pestiviruses. According to the certificate of analysis that the suppliers claimed for each batch of FBS, BVDV-1 was detected in all 11 countries and BVDV-2 was detected exclusively in the America Continent. The atypical Pestiviruses were detected in 13 batches claimed to originate from five countries. Analysis of partial 5'UTR sequences showed a high similarity among these atypical bovine Pestiviruses. This study has demonstrated, for the first time that commercial FBS batches of different geographic origins are contaminated not only with the recognised species BVDV-1 and BVDV-2, but also with the emerging atypical bovine Pestiviruses.
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virus recovery and full length sequence analysis of atypical bovine pestivirus th 04_khonkaen
Veterinary Microbiology, 2009Co-Authors: Lihong Liu, Sándor Belák, Jaruwan Kampa, Claudia BauleAbstract:Phylogenetic analysis of recently identified “atypical” bovine Pestiviruses, performed based on different gene regions, has revealed unclear relationships with other established species, therefore, their phylogenetic position could not be determined so far. In this study, the atypical pestivirus Th/04_KhonKaen was recovered from serum of a naturally infected calf and the complete genome sequence was determined and analysed, as means to define its position. The viral genome is 12,337 nucleotides (nt) long, and comprises a 5′-UTR of 383 nt, a 3′-UTR of 254 nt and an open reading frame of 11,700 nt, without duplication of viral sequences or insertions of cellular sequences. The phylogenetic analyses of the full-length sequence, performed by Neighbor-joining, Maximum likelihood, and the Bayesian approach, unanimously placed Th/04_KhonKaen in a single lineage, distinct from the established pestivirus species, and close to bovine viral diarrhea virus types 1 and 2. Furthermore, Th/04_KhonKaen and two previously reported atypical Pestiviruses D32/00_‘HoBi’ and CH-KaHo/cont formed a well-supported monophyletic clade in trees based on the complete Npro and E2 gene regions. The finding provides conclusive classification of the Th/04_KhonKaen virus and confirms the standing of the “atypical” bovine Pestiviruses as a novel pestivirus species.
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maximum likelihood and bayesian analyses of a combined nucleotide sequence dataset for genetic characterization of a novel pestivirus sva cont 08
Archives of Virology, 2009Co-Authors: Lihong Liu, Claudia Baule, Hongyan Xia, Sándor BelákAbstract:Bovine viral diarrhoea virus 1 (BVDV-1) and Bovine viral diarrhoea virus 2 (BVDV-2) are two recognised bovine pestivirus species of the genus Pestivirus. Recently, a pestivirus, termed SVA/cont-08, was detected in a batch of contaminated foetal calf serum originating from South America. Comparative sequence analysis showed that the SVA/cont-08 virus shares 15–28% higher sequence identity to pestivirus D32/00_‘HoBi’ than to members of BVDV-1 and BVDV-2. In order to reveal the phylogenetic relationship of SVA/cont-08 with other Pestiviruses, a molecular dataset of 30 Pestiviruses and 1,896 characters, comprising the 5′UTR, Npro and E2 gene regions, was analysed by two methods: maximum likelihood and Bayesian approach. An identical, well-supported tree topology was observed, where four Pestiviruses (SVA/cont-08, D32/00_‘HoBi’, CH-KaHo/cont, and Th/04_KhonKaen) formed a monophyletic clade that is closely related to the BVDV-1 and BVDV-2 clades. The strategy applied in this study is useful for classifying novel Pestiviruses in the future.
Julia F. Ridpath - One of the best experts on this subject based on the ideXlab platform.
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serological survey for antibodies against Pestiviruses in wyoming domestic sheep
Veterinary Microbiology, 2018Co-Authors: Simone Silveira, Julia F. Ridpath, Shollie M Falkenberg, M J Elderbrook, K S Sondgeroth, Rohana P Dassanayake, John D Neill, Claudio Wageck CanalAbstract:Pestiviruses including Bovine viral diarrhea virus type 1 (BVDV-1), BVDV-2 and Border disease virus (BDV) have been reported in both sheep and cattle populations, together with the HoBi-like, an emerging group of Pestiviruses. Pestivirus control programs in the United States have focused on the control of BVDV-1 and 2. The incidence of pestivirus infection in sheep in the United States and the risk of transmission between cattle and sheep populations are unknown. The aim of this study was to perform serological surveillance for pestivirus exposure in sheep from an important sheep producing state in the Unites States, Wyoming. For this, sera from 500 sheep, collected across the state of Wyoming (US) in 2015-2016, were examined by comparative virus neutralization assay against four species/proposed species of Pestiviruses: BVDV-1, BVDV-2, BDV and HoBi-like virus. Rates of exposure varied between geographic regions within the state. The overall pestivirus prevalence of antibodies was 5.6%. Antibodies were most frequently detected against BVDV-1 (4%), and the highest antibody titers were also against BVDV-1. Data from this study highlights understanding of the dynamics of sheep pestivirus exposure, consideration of reference strains used for VN assays, transmission patterns, and potential vaccination history should be taken into account in implementation of control measures against Pestiviruses in sheep and for successful BVDV control programs in cattle.
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A genetic profile of bovine Pestiviruses circulating in Brazil (1998-2018).
Animal health research reviews, 2018Co-Authors: Eduardo Furtado Flores, Julia F. Ridpath, Francielle Liz Monteiro, Juliana Felipetto Cargnelutti, Fernando V. Bauermann, Rudi WeiblenAbstract:The Pestiviruses bovine viral diarrhea virus 1 (BVDV-1), 2 (BVDV-2), and HoBi-like (HoBiPeV) are endemic among Brazilian cattle, the world's largest commercial bovine herd. In the last two decades (1998–2018) over 300 bovine Pestiviruses have been partially or fully sequenced in Brazil, including viruses from different regions, different epidemiological backgrounds, and associated with diverse clinical presentations. Phylogenetic analysis of these viruses demonstrated a predominance of BVDV-1 (54.4%), with subgenotypes −1a (33.9% of total) and −1b (16.3%) being more frequent and subgenotypes −1d, −1e, and −1i at very low frequencies. The overall BVDV-2 frequency was 25.7% but it varied largely by region, reaching up to 48% in Southern states. BVDV-2b was the predominant subgenotype (84.8% of BVDV-2), followed by BVDV-2a (8.86%). HoBiPeV accounted for 19.9% (61/307) of the genotyped viruses and were detected at high frequency in cattle from Northeastern states. These findings demonstrate a unique mix of pestivirus species and subgenotypes, unlike that seen in Europe or North America. The design of effective diagnostic tools, vaccines, and control programs for limiting bovine pestivirus infections in Brazil must take into consideration this unique mix of viruses. This article provides a critical review of two decades of genetic identification of Pestiviruses in Brazil.
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Challenges in Identifying and Determining the Impacts of Infection with Pestiviruses on the Herd Health of Free Ranging Cervid Populations.
Frontiers in microbiology, 2016Co-Authors: Julia F. Ridpath, John D NeillAbstract:Although most commonly associated with the infection of domestic livestock, the replication of Pestiviruses, in particular the two species of bovine viral diarrhea virus (BVDV), occurs in a wide range of free ranging cervids including white-tailed deer, mule deer, fallow deer, elk, red deer, roe deer, eland and mousedeer. While virus isolation and serologic analyses indicate that Pestiviruses are circulating in these populations, little is known regarding their impact. The lack of regular surveillance programs, challenges in sampling wild populations, and scarcity of tests and vaccines compound the difficulties in detecting and controlling pestivirus infections in wild cervids. Improved detection rests upon the development and validation of tests specific for use with cervid samples and development and validation of tests that reliably detect emerging Pestiviruses. Estimation of impact of pestivirus infections on herd health will require the integration of several disciplines including epidemiology, cervid natural history, veterinary medicine, pathology and microbiology.
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clinical presentation resembling mucosal disease associated with hobi like pestivirus in a field outbreak
Transboundary and Emerging Diseases, 2016Co-Authors: M N Weber, Julia F. Ridpath, A C S Mosena, Sara Vilar Dantas Simoes, Laura Lopes De Almeida, Clarice R M Pessoa, Renata Da Fontoura Budaszewski, Tatiane Rodrigues Da Silva, Franklin Rietcorrea, David DriemeierAbstract:The genus Pestivirus of the family Flaviviridae consists of four recognized species: Bovine viral diarrhoea virus 1 (BVDV-1), Bovine viral diarrhoea virus 2 (BVDV-2), Classical swine fever virus (CSFV) and Border disease virus (BDV). Recently, atypical Pestiviruses ('HoBi'-like Pestiviruses) were identified in batches of contaminated foetal calf serum and in naturally infected cattle with and without clinical symptoms. Here, we describe the first report of a mucosal disease-like clinical presentation (MD) associated with a 'HoBi'-like pestivirus occurring in a cattle herd. The outbreak was investigated using immunohistochemistry, antibody detection, viral isolation and RT-PCR. The sequence and phylogenetic analysis of 5'NCR, N(pro) and E2 regions of the RT-PCR positive samples showed that four different 'HoBi'-like strains were circulating in the herd. The main clinical signs and lesions were observed in the respiratory and digestive systems, but skin lesions and corneal opacity were also observed. MD characteristic lesions and a pestivirus with cytopathic biotype were detected in one calf. The present study is the first report of a MD like presentation associated with natural infection with 'HoBi'-like pestivirus. This report describes the clinical signs and provides a pathologic framework of an outbreak associated with at least two different 'HoBi'-like strains. Based on these observations, it appears that these atypical Pestiviruses are most likely underdiagnosed in Brazilian cattle.
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Pestiviruses: old enemies and new challenges.
Animal health research reviews, 2015Co-Authors: Julia F. Ridpath, John D NeillAbstract:The genesis for this special issue on Pestiviruses was a joint meeting on Pestiviruses organized by the US BVDV Symposia Committee and the European Society for Veterinary Virology that was held October 14 and 15, 2014 in Kansas City, MO. The theme of the meeting was "Pestiviruses: Old enemies and new challenges". The impetus for this joint effort was the recognition that regional approaches to disease control are at odds with the worldwide traffic in animal products and biologics. Further, the control of newly recognized Pestiviruses, such as HoBi-like viruses, is more effective when approached as a global challenge rather than any one nation's problem. The joint meeting featured talks by researchers from North America, South America, Australia and Europe. The papers in this issue arose from keynote talks presented at the joint meeting and are organized around the following themes; Pestiviruses and the immune system, genetic variability, the emergence of new Pestiviruses and pestivirus control programs.
Claudia Baule - One of the best experts on this subject based on the ideXlab platform.
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Effects of methodology and analysis strategy on robustness of pestivirus phylogeny
Virus Research, 2009Co-Authors: Claudia Baule, Sándor Belák, Niklas WahlbergAbstract:Abstract Phylogenetic analysis of Pestiviruses is a useful tool for classifying novel Pestiviruses and for revealing their phylogenetic relationships. In this study, robustness of pestivirus phylogenies has been compared by analyses of the 5′UTR, and complete N pro and E2 gene regions separately and combined, performed by four methods: neighbour-joining (NJ), maximum parsimony (MP), maximum likelihood (ML), and Bayesian inference (BI). The strategy of analysing the combined sequence dataset by BI, ML, and MP methods resulted in a single, well-supported tree topology, indicating a reliable and robust pestivirus phylogeny. By contrast, the single-gene analysis strategy resulted in 12 trees of different topologies, revealing different relationships among Pestiviruses. These results indicate that the strategies and methodologies are two vital aspects affecting the robustness of the pestivirus phylogeny. The strategy and methodologies outlined in this paper may have a broader application in inferring phylogeny of other RNA viruses.
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virus recovery and full length sequence analysis of atypical bovine pestivirus th 04_khonkaen
Veterinary Microbiology, 2009Co-Authors: Lihong Liu, Sándor Belák, Jaruwan Kampa, Claudia BauleAbstract:Phylogenetic analysis of recently identified “atypical” bovine Pestiviruses, performed based on different gene regions, has revealed unclear relationships with other established species, therefore, their phylogenetic position could not be determined so far. In this study, the atypical pestivirus Th/04_KhonKaen was recovered from serum of a naturally infected calf and the complete genome sequence was determined and analysed, as means to define its position. The viral genome is 12,337 nucleotides (nt) long, and comprises a 5′-UTR of 383 nt, a 3′-UTR of 254 nt and an open reading frame of 11,700 nt, without duplication of viral sequences or insertions of cellular sequences. The phylogenetic analyses of the full-length sequence, performed by Neighbor-joining, Maximum likelihood, and the Bayesian approach, unanimously placed Th/04_KhonKaen in a single lineage, distinct from the established pestivirus species, and close to bovine viral diarrhea virus types 1 and 2. Furthermore, Th/04_KhonKaen and two previously reported atypical Pestiviruses D32/00_‘HoBi’ and CH-KaHo/cont formed a well-supported monophyletic clade in trees based on the complete Npro and E2 gene regions. The finding provides conclusive classification of the Th/04_KhonKaen virus and confirms the standing of the “atypical” bovine Pestiviruses as a novel pestivirus species.
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maximum likelihood and bayesian analyses of a combined nucleotide sequence dataset for genetic characterization of a novel pestivirus sva cont 08
Archives of Virology, 2009Co-Authors: Lihong Liu, Claudia Baule, Hongyan Xia, Sándor BelákAbstract:Bovine viral diarrhoea virus 1 (BVDV-1) and Bovine viral diarrhoea virus 2 (BVDV-2) are two recognised bovine pestivirus species of the genus Pestivirus. Recently, a pestivirus, termed SVA/cont-08, was detected in a batch of contaminated foetal calf serum originating from South America. Comparative sequence analysis showed that the SVA/cont-08 virus shares 15–28% higher sequence identity to pestivirus D32/00_‘HoBi’ than to members of BVDV-1 and BVDV-2. In order to reveal the phylogenetic relationship of SVA/cont-08 with other Pestiviruses, a molecular dataset of 30 Pestiviruses and 1,896 characters, comprising the 5′UTR, Npro and E2 gene regions, was analysed by two methods: maximum likelihood and Bayesian approach. An identical, well-supported tree topology was observed, where four Pestiviruses (SVA/cont-08, D32/00_‘HoBi’, CH-KaHo/cont, and Th/04_KhonKaen) formed a monophyletic clade that is closely related to the BVDV-1 and BVDV-2 clades. The strategy applied in this study is useful for classifying novel Pestiviruses in the future.
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Virus recovery and full-length sequence analysis of atypical bovine pestivirus Th/04_KhonKaen
Veterinary Microbiology, 2009Co-Authors: Lihong Liu, Sándor Belák, Jaruwan Kampa, Claudia BauleAbstract:Phylogenetic analysis of recently identified bovine “atypical” Pestiviruses, performed based on different gene regions, has revealed unclear relationships with other established species, therefore, their phylogenetic position could not been determined so far. In this study, the atypical pestivirus Th/04_KhonKaen was recovered from serum of a naturally infected calf and the complete genome sequence was determined and analysed, as means to define its position. The viral genome is 12 337 nucleotides (nt) long, and comprises a 5′ UTR of 383 nt, a 3′ UTR of 254 nt and an open reading frame of 11700 nt, without duplication of viral sequences or insertions of cellular sequences. The phylogenetic analyses of the full-length sequence, performed by Neighbor-joining, maximum likelihood, and the Bayesian approach, unanimously placed Th/04_KhonKaen in a single lineage, distinct from the established pestivirus species, and close to bovine viral diarrhea virus types 1 and 2. Furthermore, Th/04_KhonKaen and two previously reported atypical Pestiviruses D32/00_‘HoBi' and CH-KaHo/cont formed a well-supported monophyletic clade in trees based on the complete N and E2 gene regions. The finding provides conclusive classification of the Th/04_KhonKaen virus and confirms the standing of the bovine “atypical” Pestiviruses as a novel pestivirus species.
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Phylogeny, classification and evolutionary insights into Pestiviruses.
Virology, 2009Co-Authors: Lihong Liu, Niklas Wahlberg, Sándor Belák, Hongyan Xia, Claudia BauleAbstract:Abstract The genus Pestivirus comprises four established species: Bovine viral diarrhoea viruses 1 (BVDV-1) and 2 (BVDV-2), Border disease virus (BDV), and Classical swine fever virus (CSFV); and a tentative species, Pestivirus of giraffe. Additional Pestiviruses have been identified and suggested for recognition as novel subgroups/species. To achieve a reliable phylogeny as the basis for classification of Pestiviruses, a molecular dataset of 56 Pestiviruses and 2089 characters, comprising the 5′UTR, complete Npro and E2 gene regions was analysed by Maximum likelihood and Bayesian approach. An identical, robust tree topology was inferred, where seven well-supported monophyletic clades and two highly divergent lineages were identified. Dating most recent common ancestor was estimated for major pestivirus lineages and their evolutionary histories were revealed. Accordingly, a new proposal is presented for the classification of Pestiviruses into nine species: BVDV-1, BVDV-2, BVDV-3 (atypical bovine Pestiviruses), Pestivirus of giraffe, CSFV, BDV, Tunisian sheep virus (TSV; previously termed “Tunisian isolates”), Antelope and Bungowannah.