Adaptive evolution of West Nile virus facilitated increased transmissibility and prevalence in New York State
Creators: name: Bialosuknia, Sean M.
name: Dupuis, Alan P.
name: Zink, Steven D.
name: Koetzner, Cheri A.
name: Maffei, Joseph G.
name: Owen, Jennifer C.
name: Landwerlen, Hannah
name: Kramer, Laura D.
name: Ciota, Alexander T.
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Evolutionary Biology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: Ecology
subject: 69999 Biological Sciences not elsewhere classified
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: 110309 Infectious Diseases
subject: 60506 Virology
subject: Computational Biology

description: West Nile virus (WNV; <i>Flavivirus</i>, <i>Flaviviridae</i>) was introduced to New York State (NYS) in 1999 and rapidly expanded its range through the continental United States (US). NY10, an emergent genotype characterized by shared amino acid substitutions R1331 K and I2513M, appears in the genetic record of NYS WNV strains in 2010 and coincides with increased WNV cases in humans and an increased prevalence of the virus in mosquitoes. Excepting the displacement of the WN02 genotype by the NY99 genotype, there has been little evidence of adaptive evolution of WNV in the US. Previous data demonstrated increased prevalence of NY10 strains and evidence of positive selection. We expand our investigation of the surveillance record of WNV and investigate if NY10 genotype strains are associated with phenotypic change consistent with an adaptive advantage. WNV has shown a significant increase in prevalence in mosquito pools tested by NYS arbovirus surveillance, and updated sequencing of more recent mosquito pools shows a continued dominance of NY10. We tested NY10 strains <i>in vivo</i> in <i>Culex pipiens</i> mosquitoes to assess infectivity and transmissibility and found that the NY10 genotype strains infect a greater number of mosquitoes at a lower dose and are more transmissible than WN02. Experimental infection of American robins (<i>Turdus migratorius</i>) was done to assess <i>in vivo</i> viremia kinetics of NY10 relative to WN02. Modeling the increased infectivity and transmissibility of the NY10 strains together with strain-specific viremia demonstrates a mechanistic basis for selection that has likely contributed to the increased prevalence of WNV in NYS. Previous assessment of WNV evolution in NYS revealed mutations in the WNV genome with evidence of positive selection that emerged coincident with increasing WNV activity, indicating potential for an adaptive advantage. To examine whether the increase in WNV activity in NYS could be driven by NY10 mutations, we assessed the ability of distinct NY10 strains to infect and be transmitted by <i>Culex pipiens</i>, the primary vector of WNV in the Northeast US. indicate that NY10 strains are more infectious and transmissible than the ancestral WN02 genotype strain at the same dose. Additionally, we experimentally infected American robins to assess differences in viral replication <i>in vivo</i>. Modeling the increased infectivity and transmissibility of the NY10 genotype demonstrates a mechanistic basis for selection that has likely contributed to the increased prevalence of WNV in NYS.