Host proteostasis modulates influenza evolution
| Autor: | Sean M. McHugh, Leonid A. Mirny, Vincent L. Butty, Angela M Phillips, Anna I. Ponomarenko, Emmanuel E Nekongo, Stuart S. Levine, Matthew D. Shoulders, Yu-Shan Lin, Luna O Gonzalez |
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| Přispěvatelé: | Institute for Medical Engineering and Science, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Department of Mathematics, Massachusetts Institute of Technology. Department of Physics, Phillips, Angela Marie, Gonzalez, Luna O., Nekongo, Emmanuel E, Ponomarenko, Anna, Butty, Vincent L G, Levine, Stuart S., Mirny, Leonid A, Shoulders, Matthew D. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mutation rate Viral protein QH301-705.5 Science selection Genomics Hsp90 medicine.disease_cause General Biochemistry Genetics and Molecular Biology Madin Darby Canine Kidney Cells Evolution Molecular mutational landscape Viral Proteins 03 medical and health sciences Dogs heat shock response Biochemistry and Chemical Biology None Evolution of influenza medicine Animals Selection Genetic Biology (General) Genetics General Immunology and Microbiology biology Influenza A Virus H3N2 Subtype General Neuroscience RNA RNA virus General Medicine biology.organism_classification 3. Good health 030104 developmental biology Proteostasis heat shock factor 1 Genomics and Evolutionary Biology Viral evolution Host-Pathogen Interactions Mutation Medicine Genetic Fitness Research Article |
| Zdroj: | eLife eLife, Vol 6 (2017) |
| Popis: | 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. National Institutes of Health (U.S.) (Award 1DP2GM119162) National Institutes of Health (U.S.) (Grant P30-ES002109) |
| Databáze: | OpenAIRE |
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