Tradeoffs for a viral mutant with enhanced replication speed

Matthew R. Lanahan, Robert W. Maples, Julie K. Pfeiffer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

RNA viruses exist as genetically heterogeneous populations due to high mutation rates, and many of these mutations reduce fitness and/or replication speed. However, it is unknown whether mutations can increase replication speed of a virus already well adapted to replication in cultured cells. By sequentially passaging coxsackievirus B3 in cultured cells and collecting the very earliest progeny, we selected for increased replication speed. We found that a single mutation in a viral capsid protein, VP1-F106L, was sufficient for the fast-replication phenotype. Characterization of this mutant revealed quicker genome release during entry compared to wild-type virus, highlighting a previously unappreciated infection barrier. However, this mutation also reduced capsid stability in vitro and reduced replication and pathogenesis in mice. These results reveal a tradeoff between overall replication speed and fitness. Importantly, this approach—selecting for the earliest viral progeny—could be applied to a variety of viral systems and has the potential to reveal unanticipated inefficiencies in viral replication cycles.

Original languageEnglish (US)
Article numbere2105288118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number30
DOIs
StatePublished - Jul 27 2021

Keywords

  • Capsid
  • Coxsackievirus
  • Fitness
  • Replication speed

ASJC Scopus subject areas

  • General

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