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The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and...

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Autores principales: Fernández de Marco, María del Mar, Alejo, Alí, Hudson, Paul, Damon, Inger K., Alcami, Antonio
Formato: Texto
Lenguaje:English
Publicado: The Federation of American Societies for Experimental Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857867/
https://www.ncbi.nlm.nih.gov/pubmed/20019241
http://dx.doi.org/10.1096/fj.09-144733
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author Fernández de Marco, María del Mar
Alejo, Alí
Hudson, Paul
Damon, Inger K.
Alcami, Antonio
author_facet Fernández de Marco, María del Mar
Alejo, Alí
Hudson, Paul
Damon, Inger K.
Alcami, Antonio
author_sort Fernández de Marco, María del Mar
collection PubMed
description Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.
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spelling pubmed-28578672010-05-06 The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon Fernández de Marco, María del Mar Alejo, Alí Hudson, Paul Damon, Inger K. Alcami, Antonio FASEB J Research Communications Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. The Federation of American Societies for Experimental Biology 2010-05 /pmc/articles/PMC2857867/ /pubmed/20019241 http://dx.doi.org/10.1096/fj.09-144733 Text en © 2010 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Communications
Fernández de Marco, María del Mar
Alejo, Alí
Hudson, Paul
Damon, Inger K.
Alcami, Antonio
The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title_full The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title_fullStr The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title_full_unstemmed The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title_short The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
title_sort highly virulent variola and monkeypox viruses express secreted inhibitors of type i interferon
topic Research Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857867/
https://www.ncbi.nlm.nih.gov/pubmed/20019241
http://dx.doi.org/10.1096/fj.09-144733
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