Host proteostasis modulates influenza evolution
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elife-28652-v1.pdf
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3.01 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
McHugh, Sean M
Lin, Yu-Shan
Phillips, Angela Marie
Gonzalez, Luna O.
Nekongo, Emmanuel E
Ponomarenko, Anna
Butty, Vincent L G
Levine, Stuart S.
Mirny, Leonid A
Shoulders, Matthew D.
Date Issued
September 2017
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Phillips, Angela M et al. “Host Proteostasis Modulates Influenza Evolution.” eLife 6 (September 2017): e28652 © Phillips et al
Version
Final published version
Abstract
Predicting and constraining RNA virus evolution require understanding the molecular factors that define the mutational landscape accessible to these pathogens. RNA viruses typically have high mutation rates, resulting in frequent production of protein variants with compromised biophysical properties. Their evolution is necessarily constrained by the consequent challenge to protein folding and function. We hypothesized that host proteostasis mechanisms may be significant determinants of the fitness of viral protein variants, serving as a critical force shaping viral evolution. Here, we test that hypothesis by propagating influenza in host cells displaying chemically-controlled, divergent proteostasis environments. We find that both the nature of selection on the influenza genome and the accessibility of specific mutational trajectories are significantly impacted by host proteostasis. These findings provide new insights into features of host-pathogen interactions that shape viral evolution, and into the potential design of host proteostasis-targeted antiviral therapeutics that are refractory to resistance.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Mathematics
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/eLife.28652
