The emergence of NY10: insights into the 2012 West Nile Virus outbreak in the United States

Abstract

West Nile Virus (WNV) remains a public health risk across North America due to its capacity for rapid adaptation and evolution. While research in the United States has focused on the WN02 and SW03 mutations, the NY10 genotype, first detected in 2010, has received comparatively little attention. We conducted a phylogenetic and phylodynamic investigation of NY10, revealing its rapid increase in detection frequency and effective population size in the early 2010s. Our analysis suggests that NY10 played an important role in the 2012 WNV outbreak, with an effective population size indicating higher diversity than other lineages during this period. Despite this, NY10 appears geographically restricted, with no detections west of Colorado, indicating that barriers in the southwestern United States may influence its spread. These findings highlight the complex interplay between viral evolution, geography, and the environmental factors that shape WNV epidemiology. The study emphasizes the potential of WNV to generate genotypes with epidemic potential and underscores the importance of integrating genetic data into surveillance and forecasting systems to better predict and manage future outbreaks. Understanding the drivers of WNV's genetic diversity will be crucial for developing more effective public health strategies as the virus continues to evolve.

Keywords: NY10; WNV; West Nile virus; arbovirus; phylogenetic analysis.

Figure 1

Time-scaled phylogenetic trees of WNV annotated with NY10 associated mutations. a) Approximate maximum-likelihood tree of all publicly available WNV genomes with county-level geolocation data, from 1999-2020. Purple dotted line denotes the timepoint of the first detection of NY10. Black star denotes the most recent common ancestor of all NY10 genomes, genomes which were used to construct Bayesian phylogeny. For both trees, purple leaf nodes denote genomes with NY10 genotype (both NS2A-R188K and NS4B-I240M), blue leaf nodes denote NS2A-R188K only, and yellow leaf nodes denote NS4B-I240M only. b) Bayesian phylogeny showing the origins of NY10. Black star denotes the most recent common ancestor of the NY10 lineage with its parent clade labelled on the exterior of the tree.

Figure 2

Distribution of the NY10 genotype and NY10-associated mutations, 2012-2020. Size of circles represents the number of genomes in our full dataset (min. 1, max. 97) at the county-level, coloured by genotype. Pie charts placed at county centroid.

Figure 3

NY10 lineage and the southwest subclade. a) Pruned subtree from phylogeny in Fig. 1b, showing only the NY10 lineage, and annotated by state of origin. Black star denotes the southwest subclade. b) Most common nonsynonymous mutations within the southwest subclade listed along top. NY10 mutations coloured in purple, and SW03 mutations bolded for emphasis. boxes represent presence/absence of the given mutation.

Figure 4

Temporal trends in NY10 genotype sampling frequency and associated population dynamics of the NY10 lineage. All figures represent trends only for counties where the NY10 genotype has been observed. a) Percentage of genomes with NY10 genotype by year. Grey bar plot at bottom shows number of samples available in our dataset for each year. b) Results of two SkyGrid models estimating log effective population size for the NY10 lineage in purple, and all genomes outside the NY10 lineage and its parental clade in green. Points represent median at each timepoint. Shaded regions represent 95% HPD intervals. c) Results of two BDSKY models estimating effective reproduction number for the same populations in panel b, with points representing median for the proceeding 6-month period. Shaded regions represent 95% HPD intervals. For b) and c) labels on the x-axis represent January 1 of the listed year.

Figure 5

Qualitative comparison of 2012 outbreak geographic distribution. a) County-level year-over-year case incidence of WNND for 2012, with known spatial distribution of NY10 genotype overlaid (2012-2020 genomic data). b) Longitudinal distribution of WNND in 2012 (red) and 2011(grey).