MIT Libraries homeMIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones

Author(s)
Phillips, Angela Marie; Ponomarenko, Anna; Chen, Kenny; Butty, Vincent L G; Whittaker, Charles A.; Moore, Christopher Lawrence; Shoulders, Matthew D.; ... Show more Show less
Thumbnail
DownloadPublished version (3.330Mb)
Terms of use
Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
Metadata
Show full item record
Abstract
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.
Date issued
2018-09
URI
https://hdl.handle.net/1721.1/125570
Department
Massachusetts Institute of Technology. Department of Chemistry; David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
Journal
PLoS biology
Publisher
Public Library of Science (PLoS)
Citation
Phillips, Angela M. et al. “Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones.” PLoS biology 16 (2018): e3000008 © 2018 The Author(s)
Version: Final published version
ISSN
1544-9173

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries homeMIT Libraries logo

Find us on

Twitter Facebook Instagram YouTube RSS

MIT Libraries navigation

SearchHours & locationsBorrow & requestResearch supportAbout us
PrivacyPermissionsAccessibility
MIT
Massachusetts Institute of Technology
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.