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In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innat...

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Autores principales: Deeg, Christoph M., Hassan, Ebrahim, Mutz, Pascal, Rheinemann, Lara, Götz, Veronika, Magar, Linda, Schilling, Mirjam, Kallfass, Carsten, Nürnberger, Cindy, Soubies, Sébastien, Kochs, Georg, Haller, Otto, Schwemmle, Martin, Staeheli, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413327/
https://www.ncbi.nlm.nih.gov/pubmed/28396461
http://dx.doi.org/10.1084/jem.20161033
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author Deeg, Christoph M.
Hassan, Ebrahim
Mutz, Pascal
Rheinemann, Lara
Götz, Veronika
Magar, Linda
Schilling, Mirjam
Kallfass, Carsten
Nürnberger, Cindy
Soubies, Sébastien
Kochs, Georg
Haller, Otto
Schwemmle, Martin
Staeheli, Peter
author_facet Deeg, Christoph M.
Hassan, Ebrahim
Mutz, Pascal
Rheinemann, Lara
Götz, Veronika
Magar, Linda
Schilling, Mirjam
Kallfass, Carsten
Nürnberger, Cindy
Soubies, Sébastien
Kochs, Georg
Haller, Otto
Schwemmle, Martin
Staeheli, Peter
author_sort Deeg, Christoph M.
collection PubMed
description Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population.
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spelling pubmed-54133272017-11-01 In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein Deeg, Christoph M. Hassan, Ebrahim Mutz, Pascal Rheinemann, Lara Götz, Veronika Magar, Linda Schilling, Mirjam Kallfass, Carsten Nürnberger, Cindy Soubies, Sébastien Kochs, Georg Haller, Otto Schwemmle, Martin Staeheli, Peter J Exp Med Research Articles Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population. The Rockefeller University Press 2017-05-01 /pmc/articles/PMC5413327/ /pubmed/28396461 http://dx.doi.org/10.1084/jem.20161033 Text en © 2017 Deeg et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Deeg, Christoph M.
Hassan, Ebrahim
Mutz, Pascal
Rheinemann, Lara
Götz, Veronika
Magar, Linda
Schilling, Mirjam
Kallfass, Carsten
Nürnberger, Cindy
Soubies, Sébastien
Kochs, Georg
Haller, Otto
Schwemmle, Martin
Staeheli, Peter
In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title_full In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title_fullStr In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title_full_unstemmed In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title_short In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
title_sort in vivo evasion of mxa by avian influenza viruses requires human signature in the viral nucleoprotein
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413327/
https://www.ncbi.nlm.nih.gov/pubmed/28396461
http://dx.doi.org/10.1084/jem.20161033
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