Evolutionary influences on the reduction in enzootic circulation and human incidence of western equine encephalitis

Understanding the evolutionary and ecological circumstances in which arboviruses emerge into naïve geographical areas is critical for the development of targeted maintenance and prevention strategies. In order to develop a complete understanding of the ways in which viruses emerge, the factors surrounding a reduction in virus activity, or submergence, must also be studied. Western equine encephalitis virus (WEEV) provides a unique case study on how submergence can be understood by observing evolutionary and ecological factors. WEEV caused several epizootic events in the early 20th century that account for the death of thousands humans and equids. Later in the century, the number of reported cases dropped with the last human case occurring in 1998. However, WEEV has still been detected in mosquito, albeit at reduced levels. My studies identified six nonsynonymous mutations that were phylogenetically significant for the evolution of WEEV through the 20th century. I also found that these mutations have a phenotypic effect on WEEV’s enzootic hosts. Using competitive fitness assays, contemporary mutations have a competitive advantage in Culex tarsalis and possibly house sparrows. Additionally, these mutations have no effect on virulence in the Syrian golden hamster. Given this data I propose that the mutations WEEV has accumulated by positive selection only enhance this ability to transmit enzootically. I also hypothesize the mutations that confer mammalian virulence were purified out of the population by negative selection due to a reduction in selective pressure on those residues. Overall, the evolution of WEEV over the 20th century trends away from disease in mammals and toward its enzootic cycle. A number of factors could account for this ranging from the vaccination and drastic reduction of the US equine population, the use of screens on windows and doors, and/or changes in agricultural practices. The submergence of WEEV was likely precipitated by an ecological shift critical for the virus’ maintenance of the mutations that confer virulence in mammals and subsequently compensated by increasing its adaptability to its enzootic hosts. However, these compensatory mutations may be an example of too little too late as evidenced by the subsequent decline in population size.