tetano
Editor, Senior Moderator
Elife. 2017 Sep 26;6. pii: e28652. doi: 10.7554/eLife.28652.
[h=1]Host proteostasis modulates influenza evolution.[/h] Phillips AM[SUP]1[/SUP], Gonzalez LO[SUP]2[/SUP], Nekongo EE[SUP]1[/SUP], Ponomarenko AI[SUP]1[/SUP], McHugh SM[SUP]3[/SUP], Butty VL[SUP]4[/SUP], Levine SS[SUP]4[/SUP], Lin YS[SUP]3[/SUP], Mirny LA[SUP]5,[/SUP][SUP]6[/SUP], Shoulders MD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Hsp90; biochemistry; evolutionary biology; genomics; heat shock factor 1; heat shock response; mutational landscape; none; selection
PMID: 28949290 PMCID: PMC5614556 DOI: 10.7554/eLife.28652
Free PMC Article
[h=1]Host proteostasis modulates influenza evolution.[/h] Phillips AM[SUP]1[/SUP], Gonzalez LO[SUP]2[/SUP], Nekongo EE[SUP]1[/SUP], Ponomarenko AI[SUP]1[/SUP], McHugh SM[SUP]3[/SUP], Butty VL[SUP]4[/SUP], Levine SS[SUP]4[/SUP], Lin YS[SUP]3[/SUP], Mirny LA[SUP]5,[/SUP][SUP]6[/SUP], Shoulders MD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Hsp90; biochemistry; evolutionary biology; genomics; heat shock factor 1; heat shock response; mutational landscape; none; selection
PMID: 28949290 PMCID: PMC5614556 DOI: 10.7554/eLife.28652
Free PMC Article