tetano
Editor, Senior Moderator
PLoS Biol. 2018 Sep 17;16(9):e3000008. doi: 10.1371/journal.pbio.3000008. [Epub ahead of print]
[h=1]Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones.[/h] Phillips AM[SUP]1[/SUP], Ponomarenko AI[SUP]1[/SUP], Chen K[SUP]1[/SUP], Ashenberg O[SUP]2[/SUP], Miao J[SUP]3[/SUP], McHugh SM[SUP]3[/SUP], Butty VL[SUP]4[/SUP], Whittaker CA[SUP]4[/SUP], Moore CL[SUP]1[/SUP], Bloom JD[SUP]2[/SUP], Lin YS[SUP]3[/SUP], Shoulders MD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 30222731 DOI: 10.1371/journal.pbio.3000008
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[h=1]Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones.[/h] Phillips AM[SUP]1[/SUP], Ponomarenko AI[SUP]1[/SUP], Chen K[SUP]1[/SUP], Ashenberg O[SUP]2[/SUP], Miao J[SUP]3[/SUP], McHugh SM[SUP]3[/SUP], Butty VL[SUP]4[/SUP], Whittaker CA[SUP]4[/SUP], Moore CL[SUP]1[/SUP], Bloom JD[SUP]2[/SUP], Lin YS[SUP]3[/SUP], Shoulders MD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 30222731 DOI: 10.1371/journal.pbio.3000008
Free full text