Adaptive evolution of West Nile virus facilitated increased transmissibility and prevalence in New York State

ABSTRACT

West Nile virus (WNV; Flavivirus, Flaviviridae) was introduced to New York State (NYS) in 1999 and rapidly expanded its range through the continental United States (US). Apart from the displacement of the introductory NY99 genotype with the WN02 genotype, there has been little evidence of adaptive evolution of WNV in the US. WNV NY10, characterized by shared amino acid substitutions R1331K and I2513M, emerged in 2010 coincident with increased WNV cases in humans and prevalence in mosquitoes. Previous studies demonstrated an increase in frequency of NY10 strains in NYS and evidence of positive selection. Here, we present updated surveillance and sequencing data for WNV in NYS and investigate if NY10 genotype strains are associated with phenotypic change consistent with an adaptive advantage. Results confirm a significant increase in prevalence in mosquitoes though 2018, and updated sequencing demonstrates a continued dominance of NY10. We evaluated NY10 strains in Culex pipiens mosquitoes to assess vector competence and found that the NY10 genotype is associated with both increased infectivity and transmissibility. Experimental infection of American robins (Turdus migratorius) was additionally completed to assess viremia kinetics of NY10 relative to WN02. Modelling 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.

KEYWORDS:

• West Nile virus
• virus evolution
• arbovirus
• Flavivirus
• adaptive evolution

Acknowledgments

We thank the NYS Bureau of Communicable Disease Control and county health departments for mosquito collections. We additionally thank the Wadsworth Center Advanced Genomic Technologies Core for deep sequencing, the Wadsworth Center Tissue and Media Facility for providing media and cells, and the NYS Arbovirus Laboratory insectary staff for support and assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

SMB and ATC conceptualized the study. SMB, SDZ, and ATC curated data. SMB and ATC analyzed the data. Funding for this project was acquired by LDK and ATC. SMB, ADP, JCO and HL performed the investigation. SMB, APD, LDK, and ATC were responsible for the methodology. SMB, ADP, JCO, and ATC acted as administrators for the project. SMB, APD, SDZ, CAK, JGM, JCO, and HL curated project resources. Software utilized by SMB. ATC supervised the project. SMB validated project data and results. SMB and ATC visualized the data. SMB wrote the original draft. SMB and ATC reviewed and edited the manuscript.

Additional information

Funding

These studies were funded by the National Institutes of Health (R21 AI146856 and R01 AI1680907), the Cooperative Agreement Number U01CK000509 funded by the Centers for Disease Control and Prevention, and NSF IOS-1350772 to J.C.O. Contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services.