Host proteostasis modulates influenza evolution
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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eLife Sciences Publications, Ltd
2017
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| Online Access: | http://hdl.handle.net/1721.1/112799 https://orcid.org/0000-0002-9806-7574 https://orcid.org/0000-0001-7104-0278 https://orcid.org/0000-0002-1393-5783 https://orcid.org/0000-0002-0785-5410 https://orcid.org/0000-0002-6511-3431 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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. |
| author_sort | McHugh, Sean M |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:06:42Z |
| format | Article |
| id | mit-1721.1/112799 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:06:42Z |
| publishDate | 2017 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1127992022-10-01T08:15:52Z Host proteostasis modulates influenza evolution 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. 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 Phillips, Angela Marie Gonzalez, Luna O. Nekongo, Emmanuel E Ponomarenko, Anna Butty, Vincent L G Levine, Stuart S. Mirny, Leonid A Shoulders, Matthew D. 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) 2017-12-19T14:47:55Z 2017-12-19T14:47:55Z 2017-09 2017-05 2017-12-18T19:58:57Z Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/112799 Phillips, Angela M et al. “Host Proteostasis Modulates Influenza Evolution.” eLife 6 (September 2017): e28652 © Phillips et al https://orcid.org/0000-0002-9806-7574 https://orcid.org/0000-0001-7104-0278 https://orcid.org/0000-0002-1393-5783 https://orcid.org/0000-0002-0785-5410 https://orcid.org/0000-0002-6511-3431 http://dx.doi.org/10.7554/eLife.28652 eLife Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | 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. Host proteostasis modulates influenza evolution |
| title | Host proteostasis modulates influenza evolution |
| title_full | Host proteostasis modulates influenza evolution |
| title_fullStr | Host proteostasis modulates influenza evolution |
| title_full_unstemmed | Host proteostasis modulates influenza evolution |
| title_short | Host proteostasis modulates influenza evolution |
| title_sort | host proteostasis modulates influenza evolution |
| url | http://hdl.handle.net/1721.1/112799 https://orcid.org/0000-0002-9806-7574 https://orcid.org/0000-0001-7104-0278 https://orcid.org/0000-0002-1393-5783 https://orcid.org/0000-0002-0785-5410 https://orcid.org/0000-0002-6511-3431 |
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