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Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity
Poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (VACV) and variola. The vaccinia virus complement control protein (VCP...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195257/ https://www.ncbi.nlm.nih.gov/pubmed/21803094 http://dx.doi.org/10.1016/j.vaccine.2011.07.062 |
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author | Bernet, John Ahmad, Muzammil Mullick, Jayati Panse, Yogesh Singh, Akhilesh K. Parab, Pradeep B. Sahu, Arvind |
author_facet | Bernet, John Ahmad, Muzammil Mullick, Jayati Panse, Yogesh Singh, Akhilesh K. Parab, Pradeep B. Sahu, Arvind |
author_sort | Bernet, John |
collection | PubMed |
description | Poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (VACV) and variola. The vaccinia virus complement control protein (VCP), which inhibits complement by decaying the classical pathway C3-convertase (decay-accelerating activity), and by supporting inactivation of C3b and C4b by serine protease factor I (cofactor activity), was shown to play a role in viral pathogenesis. However, the role its individual complement regulatory activities impart in pathogenesis, have not yet been elucidated. Here, we have generated monoclonal antibodies (mAbs) that block the VCP functions and utilized them to evaluate the relative contribution of complement regulatory activities of VCP in viral pathogenesis by employing a rabbit intradermal model for VACV infection. Targeting VCP by mAbs that inhibited the decay-accelerating activity as well as cofactor activity of VCP or primarily the cofactor activity of VCP, by injecting them at the site of infection, significantly reduced VACV lesion size. This reduction however was not pronounced when VCP was targeted by a mAb that inhibited only the decay-accelerating activity. Further, the reduction in lesion size by mAbs was reversed when host complement was depleted by injecting cobra venom factor. Thus, our results suggest that targeting VCP by antibodies reduces VACV pathogenicity and that principally the cofactor activity of VCP appears to contribute to the virulence. |
format | Online Article Text |
id | pubmed-3195257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31952572011-12-15 Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity Bernet, John Ahmad, Muzammil Mullick, Jayati Panse, Yogesh Singh, Akhilesh K. Parab, Pradeep B. Sahu, Arvind Vaccine Article Poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (VACV) and variola. The vaccinia virus complement control protein (VCP), which inhibits complement by decaying the classical pathway C3-convertase (decay-accelerating activity), and by supporting inactivation of C3b and C4b by serine protease factor I (cofactor activity), was shown to play a role in viral pathogenesis. However, the role its individual complement regulatory activities impart in pathogenesis, have not yet been elucidated. Here, we have generated monoclonal antibodies (mAbs) that block the VCP functions and utilized them to evaluate the relative contribution of complement regulatory activities of VCP in viral pathogenesis by employing a rabbit intradermal model for VACV infection. Targeting VCP by mAbs that inhibited the decay-accelerating activity as well as cofactor activity of VCP or primarily the cofactor activity of VCP, by injecting them at the site of infection, significantly reduced VACV lesion size. This reduction however was not pronounced when VCP was targeted by a mAb that inhibited only the decay-accelerating activity. Further, the reduction in lesion size by mAbs was reversed when host complement was depleted by injecting cobra venom factor. Thus, our results suggest that targeting VCP by antibodies reduces VACV pathogenicity and that principally the cofactor activity of VCP appears to contribute to the virulence. Elsevier Science 2011-10-06 /pmc/articles/PMC3195257/ /pubmed/21803094 http://dx.doi.org/10.1016/j.vaccine.2011.07.062 Text en © 2011 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Bernet, John Ahmad, Muzammil Mullick, Jayati Panse, Yogesh Singh, Akhilesh K. Parab, Pradeep B. Sahu, Arvind Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title | Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title_full | Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title_fullStr | Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title_full_unstemmed | Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title_short | Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
title_sort | disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195257/ https://www.ncbi.nlm.nih.gov/pubmed/21803094 http://dx.doi.org/10.1016/j.vaccine.2011.07.062 |
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