title: Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture.
abstract: RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant's proficiency at cell entry with the other's proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, United States.|Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Katherine S
authors.identifier: http://orcid.org/0000-0002-4094-3615
authors.initials: KS
authors.lastname: Xue
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Molecular and Cellular Biology Program, University of Washington, Seattle, United States.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Hooper
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Molecular and Cellular Biology Program, University of Washington, Seattle, United States.
authors.forename: Anja R
authors.initials: AR
authors.lastname: Ollodart
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Molecular and Cellular Biology Program, University of Washington, Seattle, United States.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Dingens
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, United States.|Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Jesse D
authors.identifier: http://orcid.org/0000-0003-1267-3408
authors.initials: JD
authors.lastname: Bloom
mesh_terms: D000818:Animals; D004285:Dogs; D014644:Genetic Variation; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D061985:Madin Darby Canine Kidney Cells; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: D151G; D151N; cooperation; evolutionary biology; genomics; infectious disease; influenza; microbiology; neuraminidase; quasispecies; virus