Western equine encephalitis virus (WEEV) is a mosquito-borne alphavirus endemic to North and South America that transmits between birds (generally house sparrows) and mosquitoes (generally Culex tarsalis). Humans infected with WEEV can develop encephalitis, which can be fatal or leave survivors with permanent neurological damage; but, humans and other mammals are thought to be dead-end hosts for WEEV . In the mid-20th century, WEEV underwent a precipitous decline in both virulence and circulation (“submergence”). In collaboration with the Abraham lab (Harvard), WRCEVA has identified PCDH10 as a cellular receptor for WEEV, along with the alternate receptors VLDLR and ApoER2. During the time of submergence, WEEV lost the ability to bind VLDLR and ApoER2. Finally, WEEV recently lost binding to mammalian (but not avian!) PCDH10. The identification of the WEEV receptors and the shift in their utilization over time at least partially explains why WEEV submerged, and what we must monitor to maintain vigilance for potential re-emergence.
Link: https://doi.org/10.1038/s41586-024-07740-2
Link: https://doi.org/10.1016/j.cell.2025.03.029
The WRCEVA has also collaborated with scientists from Brazil to study the recent re-emergence of WEEV in the southern cone of South America. Phylogenetic studies suggested that the lineage responsible for the South American outbreaks represents the re-emergence of an enzootic strains circulating in the same region since the 1950s.
Link: https://doi.org/10.3201/eid3009.240530