title: A positively selected mutation in the WNV 2K peptide confers resistance to superinfection exclusion in vivo.
abstract: Molecular epidemiologic studies of North American (NA) West Nile virus (WNV; Flaviviridae, Flavivirus) have documented the displacement of the introduced NY99 genotype with WN02. In addition, these studies have shown that particular substitutions are under positive selection. One occurs in the C-terminus of the NS4A coding sequence and results in a valine to methionine substitution at position nine of the 2K peptide. 2K-V9M confers the ability to overcome superinfection exclusion in vitro. We hypothesized that WNV strains bearing 2K-V9M have higher fitness than wildtype in Culex quinquefasciatus mosquitoes. Although infection rates and viral titers were not significantly different, virus dissemination rates were significantly higher with WNV 2K-V9M. As a super-infecting virus, WNV 2K-V9M was more successful than wildtype, however, in a mixed infection, 2K-V9M was not. These data support observations that 2K-V9M confers a context-specific selective advantage in mosquitoes and provides an in vivo mechanism for its positive selection.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Arthropod-borne Infectious Diseases Laboratory; Colorado State University, Campus Delivery 1692, Fort Collins, CO 80523, USA.
authors.forename: Corey L
authors.initials: CL
authors.lastname: Campbell
authors.affiliation: Southern Research Institute, Frederick, MD 21701, USA.
authors.forename: Darci R
authors.initials: DR
authors.lastname: Smith
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Arthropod-borne Infectious Diseases Laboratory; Colorado State University, Campus Delivery 1692, Fort Collins, CO 80523, USA.
authors.forename: Irma
authors.initials: I
authors.lastname: Sanchez-Vargas
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Novartis Institute for Tropical Diseases, 10 Biopolis Road, Singapore.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Arthropod-borne Infectious Diseases Laboratory; Colorado State University, Campus Delivery 1692, Fort Collins, CO 80523, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ebel
mesh_terms: D000818:Animals; D003465:Culex / Q000821:virology*; D006801:Humans; D007303:Insect Vectors / Q000821:virology*; D020125:Mutation, Missense; D015163:Superinfection / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication; D014901:West Nile Fever / Q000821:virology*; D014902:West Nile virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D017361:Viral Nonstructural Proteins
keywords: Flavivirus; Superinfection exclusion; Vector mosquito
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