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RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence.
Title | RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Xiao, Y, IM Rouzine, Bianco, S, Acevedo, A, Goldstein, EFaul, Farkov, M, Brodsky, L, Andino, R |
Journal | Cell Host Microbe |
Volume | 19 |
Issue | 4 |
Pagination | 493-503 |
Date Published | 2016 Apr 13 |
ISSN | 1934-6069 |
Keywords | Adaptation, Physiological, Animals, DNA-Directed RNA Polymerases, Evolution, Molecular, Humans, Poliomyelitis, Poliovirus, Recombination, Genetic, RNA, Viral, Selection, Genetic, Viral Proteins, Virulence, Virus Replication |
Abstract | Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations. |
DOI | 10.1016/j.chom.2016.03.009 |
Alternate Journal | Cell Host Microbe |
PubMed ID | 27078068 |
PubMed Central ID | PMC4840895 |
Grant List | R01 AI36178 / AI / NIAID NIH HHS / United States R56 AI036178 / AI / NIAID NIH HHS / United States R01 AI036178 / AI / NIAID NIH HHS / United States N01AI40085 / AI / NIAID NIH HHS / United States R01 AI040085 / AI / NIAID NIH HHS / United States R21 AI036178 / AI / NIAID NIH HHS / United States P01 AI091575 / AI / NIAID NIH HHS / United States |