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Bishnupriya Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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bluetongue virus coat Protein VP2 contains sialic acid binding domains and vp5 resembles enveloped virus fusion Proteins
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Xing Zhang, Bishnupriya Bhattacharya, Mark S Boyce, Xiaokang Zhang, Stan Schein, Hong Z ZhouAbstract:Bluetongue virus (BTV) is transmitted by blood-feeding insects (Culicoides sp.) and causes hemorrhagic diseases in livestock. BTV is a nonenveloped, double-stranded RNA (dsRNA) virus with two capsids: a well-studied, stable core enclosing the dsRNA genome and a highly unstable, poorly studied coat responsible for host cell attachment and entry. Here, based on cryo-electron microscopy (cryoEM), we report a 7-A resolution structure of the infectious BTV virion, including the coat Proteins. We show that unlike other dsRNA viruses, the VP2 attachment trimer has a triskelion shape composed of three tip domains branching from a central hub domain. We identify three putative sialic acid-binding pockets in the hub and present supporting biochemical data indicating sugar moiety binding is important for BTV infection. Despite being a nonenveloped virus, the putative VP5 membrane penetration trimer, located slightly inward of the VP2 attachment trimer, has a central coiled-coil α-helical bundle, similar to the fusion Proteins of many enveloped viruses (e.g., HIV, herpesviruses, vesicular stomatitis virus, and influenza virus). Moreover, mapping of the amino acid sequence of VP5 to the secondary structural elements identified by cryoEM locates 15 amphipathic α-helical regions on the external surface of each VP5 trimer. The cryoEM density map also reveals few, weak interactions between the VP5 trimer and both the outer-coat VP2 trimer and the underlying core VP7 trimer, suggesting that the surface of VP5 could unfurl like an umbrella during penetration and shedding of the coat to release the transcriptionally active core particle.
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Interaction between Bluetongue virus outer capsid Protein VP2 and vimentin is necessary for virus egress
Virology Journal, 2007Co-Authors: Bishnupriya Bhattacharya, Rob J NoadAbstract:Background The VP2 outer capsid Protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of this outer capsid Protein on the transcriptionally active viral core would block transcription of the virus. Thus assembly of the outer capsid on the core particle must be a tightly controlled process during virus maturation. Earlier studies have detected mature virus particles associated with intermediate filaments in virus infected cells but the viral determinant for this association and the effect of disrupting intermediate filaments on virus assembly and release are unknown. Results In this study it is demonstrated that BTV VP2 associates with vimentin in both virus infected cells and in the absence of other viral Proteins. Further, the determinants of vimentin localisation are mapped to the N-terminus of the Protein and deletions of aminio acids between residues 65 and 114 are shown to disrupt VP2-vimentin association. Site directed mutation also reveals that amino acid residues Gly 70 and Val 72 are important in the VP2-vimentin association. Mutation of these amino acids resulted in a soluble VP2 capable of forming trimeric structures similar to unmodified Protein that no longer associated with vimentin. Furthermore, pharmacological disruption of intermediate filaments, either directly or indirectly through the disruption of the microtubule network, inhibited virus release from BTV infected cells. Conclusion The principal findings of the research are that the association of mature BTV particles with intermediate filaments are driven by the interaction of VP2 with vimentin and that this interaction contributes to virus egress. Furthermore, i) the N-terminal 118 amino acids of VP2 are sufficient to confer vimentin interaction. ii) Deletion of amino acids 65–114 or mutation of amino acids 70–72 to DVD abrogates vimentin association. iii) Finally, disruption of vimentin structures results in an increase in cell associated BTV and a reduction in the amount of released virus from infected cells.
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interaction between bluetongue virus outer capsid Protein VP2 and vimentin is necessary for virus egress
Virology Journal, 2007Co-Authors: Bishnupriya Bhattacharya, Rob J Noad, Polly RoyAbstract:Background The VP2 outer capsid Protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of this outer capsid Protein on the transcriptionally active viral core would block transcription of the virus. Thus assembly of the outer capsid on the core particle must be a tightly controlled process during virus maturation. Earlier studies have detected mature virus particles associated with intermediate filaments in virus infected cells but the viral determinant for this association and the effect of disrupting intermediate filaments on virus assembly and release are unknown.
Polly Roy - One of the best experts on this subject based on the ideXlab platform.
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interaction between bluetongue virus outer capsid Protein VP2 and vimentin is necessary for virus egress
Virology Journal, 2007Co-Authors: Bishnupriya Bhattacharya, Rob J Noad, Polly RoyAbstract:Background The VP2 outer capsid Protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of this outer capsid Protein on the transcriptionally active viral core would block transcription of the virus. Thus assembly of the outer capsid on the core particle must be a tightly controlled process during virus maturation. Earlier studies have detected mature virus particles associated with intermediate filaments in virus infected cells but the viral determinant for this association and the effect of disrupting intermediate filaments on virus assembly and release are unknown.
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Recombinant Baculovirus-Synthesized African Horsesickness Virus (AHSV) Outer-capsid Protein VP2 Provides Protection Against Virulent AHSV Challenge
Journal of General Virology, 1996Co-Authors: Polly Roy, David H.l. Bishop, Stephen Howard, Henry Aitchison, Baltus J. ErasmusAbstract:African horsesickness virus serotype 4 (AHSV-4) outer-capsid Proteins VP2 or VP2 and VP5, prepared from single or dual recombinant baculovirus expression vectors grown in Sf9 insect cells, were administered in different amounts to horses and the neutralizing antibody responses were measured. Control and vaccinated horses were challenged with virulent AHSV-4 6 months later and monitored post challenge. The results indicated that two inoculations of extracts containing VP2 and VP5, or VP2 alone, in doses of 5 µg VP2 or more per horse, were sufficient to elicit protection against African horsesickness (AHS) disease. The recombinant VP2 Protein is a potential candidate vaccine for AHS in horses.
Rob J Noad - One of the best experts on this subject based on the ideXlab platform.
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Interaction between Bluetongue virus outer capsid Protein VP2 and vimentin is necessary for virus egress
Virology Journal, 2007Co-Authors: Bishnupriya Bhattacharya, Rob J NoadAbstract:Background The VP2 outer capsid Protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of this outer capsid Protein on the transcriptionally active viral core would block transcription of the virus. Thus assembly of the outer capsid on the core particle must be a tightly controlled process during virus maturation. Earlier studies have detected mature virus particles associated with intermediate filaments in virus infected cells but the viral determinant for this association and the effect of disrupting intermediate filaments on virus assembly and release are unknown. Results In this study it is demonstrated that BTV VP2 associates with vimentin in both virus infected cells and in the absence of other viral Proteins. Further, the determinants of vimentin localisation are mapped to the N-terminus of the Protein and deletions of aminio acids between residues 65 and 114 are shown to disrupt VP2-vimentin association. Site directed mutation also reveals that amino acid residues Gly 70 and Val 72 are important in the VP2-vimentin association. Mutation of these amino acids resulted in a soluble VP2 capable of forming trimeric structures similar to unmodified Protein that no longer associated with vimentin. Furthermore, pharmacological disruption of intermediate filaments, either directly or indirectly through the disruption of the microtubule network, inhibited virus release from BTV infected cells. Conclusion The principal findings of the research are that the association of mature BTV particles with intermediate filaments are driven by the interaction of VP2 with vimentin and that this interaction contributes to virus egress. Furthermore, i) the N-terminal 118 amino acids of VP2 are sufficient to confer vimentin interaction. ii) Deletion of amino acids 65–114 or mutation of amino acids 70–72 to DVD abrogates vimentin association. iii) Finally, disruption of vimentin structures results in an increase in cell associated BTV and a reduction in the amount of released virus from infected cells.
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interaction between bluetongue virus outer capsid Protein VP2 and vimentin is necessary for virus egress
Virology Journal, 2007Co-Authors: Bishnupriya Bhattacharya, Rob J Noad, Polly RoyAbstract:Background The VP2 outer capsid Protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of this outer capsid Protein on the transcriptionally active viral core would block transcription of the virus. Thus assembly of the outer capsid on the core particle must be a tightly controlled process during virus maturation. Earlier studies have detected mature virus particles associated with intermediate filaments in virus infected cells but the viral determinant for this association and the effect of disrupting intermediate filaments on virus assembly and release are unknown.
Peter P. C. Mertens - One of the best experts on this subject based on the ideXlab platform.
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vaccination of horses with a recombinant modified vaccinia ankara virus mva expressing african horse sickness ahs virus major capsid Protein VP2 provides complete clinical protection against challenge
Vaccine, 2014Co-Authors: Berta Alberca, Peter P. C. Mertens, Katarzyna Bachanekbankowska, Marta Cabana, Eva Calvopinilla, Elisenda Viaplana, Lorraine Frost, Simon Gubbins, Alicia Urniza, Javier CastilloolivaresAbstract:African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the Protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice with a recombinant MVA virus expressing the major capsid Protein (VP2) of AHSV serotype 9. Vaccinated animals and a control group of unvaccinated horses were then challenged with a virulent strain of AHSV-9. The vaccinated animals were completely protected against clinical disease and also against viraemia as measured by standard end-point dilution assays. In contrast, all control horses presented viraemia after challenge and succumbed to the infection. These results demonstrate the potential of recombinant MVA viruses expressing the outer capsid VP2 of AHSV as a protective vaccine against AHSV infection in the field.
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vaccination of mice with a modified vaccinia ankara mva virus expressing the african horse sickness virus ahsv capsid Protein VP2 induces virus neutralising antibodies that confer protection against ahsv upon passive immunisation
Virus Research, 2014Co-Authors: Eva Calvopinilla, Peter P. C. Mertens, Simon Gubbins, Francisco De La Poza, Javier Ortego, Javier CastilloolivaresAbstract:Abstract In previous studies we showed that a recombinant Modified Vaccinia Ankara (MVA) virus expressing the Protein VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR−/−) against challenge. We continued these studies and determined, in the IFNAR−/− mouse model, whether the antibody responses induced by MVA-VP2 vaccination play a key role in protection against AHSV. Thus, groups of mice were vaccinated with wild type MVA (MVA-wt) or MVA-VP2 and the antisera from these mice were used in a passive immunisation experiment. Donor antisera from (a) MVA-wt; (b) MVA-VP2 vaccinated; or (c) MVA-VP2 vaccinated and AHSV infected mice, were transferred to AHSV non-immune recipient mice. The recipients were challenged with virulent AHSV together with MVA-VP2 vaccinated and MVA-wt vaccinated control animals and the levels of protection against AHSV-4 were compared between all these groups. The results showed that following AHSV challenge, mice that were passively immunised with MVA-VP2 vaccinated antisera were highly protected against AHSV disease and had lower levels of viraemia than recipients of MVA-wt antisera. Our study indicates that MVA-VP2 vaccination induces a highly protective humoral immune response against AHSV.
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Full Genome Sequencing and Genetic Characterization of Eubenangee Viruses Identify Pata Virus as a Distinct Species within the Genus Orbivirus
PLOS ONE, 2012Co-Authors: Manjunatha N Belaganahalli, Houssam Attoui, Ross A Lunt, Ian Pritchard, Joe Brownlie, Sushila Maan, Narender S. Maan, Kyriaki Nomikou, Peter D. Kirkland, Peter P. C. MertensAbstract:Eubenangee virus has previously been identified as the cause of Tammar sudden death syndrome (TSDS). Eubenangee virus (EUBV), Tilligery virus (TILV), Pata virus (PATAV) and Ngoupe virus (NGOV) are currently all classified within the Eubenangee virus species of the genus Orbivirus, family Reoviridae. Full genome sequencing confirmed that EUBV and TILV (both of which are from Australia) show high levels of aa sequence identity (>92%) in the conserved polymerase VP1(Pol), sub-core VP3(T2) and outer core VP7(T13) Proteins, and are therefore appropriately classified within the same virus species. However, they show much lower amino acid (aa) identity levels in their larger outer-capsid Protein VP2 (
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Completion of the sequence analysis and comparisons of genome segment 2 (encoding outer capsid Protein VP2) from representative isolates of the 24 bluetongue virus serotypes.
Veterinaria italiana, 2004Co-Authors: Sushila Maan, N. S. Maan, A R Samuel, R. S. O’hara, A. J. Meyer, S Rao, Peter P. C. MertensAbstract:Bluetongue (BT) is a non-contagious, arthropod-transmitted viral disease of domestic and wild ruminants. It is caused by bluetongue virus (BTV), a double-stranded (ds) RNA virus that is classified within the genus Orbivirus, family Reoviridae. There are at least twenty-four serotypes of BTV worldwide, five of which (1, 2, 4, 9 and 16) have been identified recently in Europe. BTV infects ruminants and its distribution throughout temperate and tropical regions of the world is dependent on the activity and abundance of certain vector-competent species of Culicoides midge. The outer capsid Protein VP2 of BTV is a major protective antigen and the primary determinant of virus serotype. For the first time, the authors have completed the sequence analysis of full-length VP2 genes from the reference strains of each of the 24 BTV serotypes and their amino acid sequences were deduced. Multiple alignment of the VP2 gene (Protein) sequences revealed that the level of nucleotide (amino acid) sequence variation between serotypes ranged from 29% (23%) to 59% (73%), confirming that segment 2/VP2 is the most variable BTV gene/Protein. Phylogenetic analysis of VP2 grouped together the BTV types that are known to cross-react serologically. Low identity between types was demonstrated for specific regions within the VP2 amino acid sequences that have been shown to be antigenic and play a role in virus neutralisation. The sequence data represent the completion of an important step in the creation of a comprehensive BTV sequence database, which will support more rapid molecular methods for diagnosis and identification of BTV 'types', as well as continuing molecular epidemiology and surveillance studies of BTV.
Javier Castilloolivares - One of the best experts on this subject based on the ideXlab platform.
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vaccination of horses with a recombinant modified vaccinia ankara virus mva expressing african horse sickness ahs virus major capsid Protein VP2 provides complete clinical protection against challenge
Vaccine, 2014Co-Authors: Berta Alberca, Peter P. C. Mertens, Katarzyna Bachanekbankowska, Marta Cabana, Eva Calvopinilla, Elisenda Viaplana, Lorraine Frost, Simon Gubbins, Alicia Urniza, Javier CastilloolivaresAbstract:African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the Protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice with a recombinant MVA virus expressing the major capsid Protein (VP2) of AHSV serotype 9. Vaccinated animals and a control group of unvaccinated horses were then challenged with a virulent strain of AHSV-9. The vaccinated animals were completely protected against clinical disease and also against viraemia as measured by standard end-point dilution assays. In contrast, all control horses presented viraemia after challenge and succumbed to the infection. These results demonstrate the potential of recombinant MVA viruses expressing the outer capsid VP2 of AHSV as a protective vaccine against AHSV infection in the field.
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vaccination of mice with a modified vaccinia ankara mva virus expressing the african horse sickness virus ahsv capsid Protein VP2 induces virus neutralising antibodies that confer protection against ahsv upon passive immunisation
Virus Research, 2014Co-Authors: Eva Calvopinilla, Peter P. C. Mertens, Simon Gubbins, Francisco De La Poza, Javier Ortego, Javier CastilloolivaresAbstract:Abstract In previous studies we showed that a recombinant Modified Vaccinia Ankara (MVA) virus expressing the Protein VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR−/−) against challenge. We continued these studies and determined, in the IFNAR−/− mouse model, whether the antibody responses induced by MVA-VP2 vaccination play a key role in protection against AHSV. Thus, groups of mice were vaccinated with wild type MVA (MVA-wt) or MVA-VP2 and the antisera from these mice were used in a passive immunisation experiment. Donor antisera from (a) MVA-wt; (b) MVA-VP2 vaccinated; or (c) MVA-VP2 vaccinated and AHSV infected mice, were transferred to AHSV non-immune recipient mice. The recipients were challenged with virulent AHSV together with MVA-VP2 vaccinated and MVA-wt vaccinated control animals and the levels of protection against AHSV-4 were compared between all these groups. The results showed that following AHSV challenge, mice that were passively immunised with MVA-VP2 vaccinated antisera were highly protected against AHSV disease and had lower levels of viraemia than recipients of MVA-wt antisera. Our study indicates that MVA-VP2 vaccination induces a highly protective humoral immune response against AHSV.
