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Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones
The threat of viral pandemics demands a comprehensive understanding of evolution at the host–pathogen interface. Here, we show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160216/ https://www.ncbi.nlm.nih.gov/pubmed/30222731 http://dx.doi.org/10.1371/journal.pbio.3000008 |
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author | Phillips, Angela M. Ponomarenko, Anna I. Chen, Kenny Ashenberg, Orr Miao, Jiayuan McHugh, Sean M. Butty, Vincent L. Whittaker, Charles A. Moore, Christopher L. Bloom, Jesse D. Lin, Yu-Shan Shoulders, Matthew D. |
author_facet | Phillips, Angela M. Ponomarenko, Anna I. Chen, Kenny Ashenberg, Orr Miao, Jiayuan McHugh, Sean M. Butty, Vincent L. Whittaker, Charles A. Moore, Christopher L. Bloom, Jesse D. Lin, Yu-Shan Shoulders, Matthew D. |
author_sort | Phillips, Angela M. |
collection | PubMed |
description | The threat of viral pandemics demands a comprehensive understanding of evolution at the host–pathogen interface. Here, we show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which (1) is conserved across human influenza strains, (2) confers resistance to the Myxovirus resistance protein A (MxA) restriction factor, and (3) critically contributed to adaptation to humans in the 1918 pandemic influenza strain, is rendered unfit by heat shock factor 1 inhibition–mediated host chaperone depletion at febrile temperatures. This fitness loss is due to biophysical defects that chaperones are unavailable to address when heat shock factor 1 is inhibited. Thus, influenza subverts host chaperones to uncouple the biophysically deleterious consequences of viral protein variants from the benefits of immune escape. In summary, host proteostasis plays a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host switching, and for antiviral drug development. |
format | Online Article Text |
id | pubmed-6160216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61602162018-10-19 Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones Phillips, Angela M. Ponomarenko, Anna I. Chen, Kenny Ashenberg, Orr Miao, Jiayuan McHugh, Sean M. Butty, Vincent L. Whittaker, Charles A. Moore, Christopher L. Bloom, Jesse D. Lin, Yu-Shan Shoulders, Matthew D. PLoS Biol Research Article The threat of viral pandemics demands a comprehensive understanding of evolution at the host–pathogen interface. Here, we show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which (1) is conserved across human influenza strains, (2) confers resistance to the Myxovirus resistance protein A (MxA) restriction factor, and (3) critically contributed to adaptation to humans in the 1918 pandemic influenza strain, is rendered unfit by heat shock factor 1 inhibition–mediated host chaperone depletion at febrile temperatures. This fitness loss is due to biophysical defects that chaperones are unavailable to address when heat shock factor 1 is inhibited. Thus, influenza subverts host chaperones to uncouple the biophysically deleterious consequences of viral protein variants from the benefits of immune escape. In summary, host proteostasis plays a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host switching, and for antiviral drug development. Public Library of Science 2018-09-17 /pmc/articles/PMC6160216/ /pubmed/30222731 http://dx.doi.org/10.1371/journal.pbio.3000008 Text en © 2018 Phillips et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Phillips, Angela M. Ponomarenko, Anna I. Chen, Kenny Ashenberg, Orr Miao, Jiayuan McHugh, Sean M. Butty, Vincent L. Whittaker, Charles A. Moore, Christopher L. Bloom, Jesse D. Lin, Yu-Shan Shoulders, Matthew D. Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title | Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title_full | Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title_fullStr | Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title_full_unstemmed | Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title_short | Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
title_sort | destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160216/ https://www.ncbi.nlm.nih.gov/pubmed/30222731 http://dx.doi.org/10.1371/journal.pbio.3000008 |
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