-

nihao guest [ sign in / register ]
2024-3-29 21:10:20


Phillips AM, etc.,al. Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones. PLoS Biol. 2018 Sep 17;16(9):e3000008
submited by kickingbird at Sep, 20, 2018 10:41 AM from PLoS Biol. 2018 Sep 17;16(9):e3000008

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.

See Also:

Latest articles in those days:

[Go Top]    [Close Window]

Related Pages:
Learn about the flu news, articles, events and more
Subscribe to the weekly F.I.C newsletter!


  

Site map  |   Contact us  |  Term of use  |  FAQs |  粤ICP备10094839号-1
Copyright ©www.flu.org.cn. 2004-2024. All Rights Reserved. Powered by FIC 4.0.1
  Email:webmaster@flu.org.cn