Pathogenesis and transmission of Venezuelan equine encephalitis virus

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Venezuelan equine encephalitis virus (VEEV) is an emerging arboviral pathogen that affects the Americas. Outbreaks can involve hundreds- of- thousands of equines and humans, spread over large geographic regions, and can last several years. The principal vector in most major coastal outbreaks is the mosquito Aedes taeniorhynchus. This species is more susceptible to most epidemic than to enzootic strains, and the adaptation of VEEV to this vector may be an important determinant of epidemic transmission. However, studies on the infection, dissemination, and transmission of VEEV regarding this important vector are lacking. \r\nThe major determinant of Ae. taeniorhynchus infection with VEEV is the E2 envelope glycoprotein, which interacts with cellular receptors. I therefore hypothesized that differential interactions of VEEV with receptors on midgut epithelial cells determine the ability of a representative epidemic versus a representative enzootic strain to infect this mosquito. In support of this hypothesis, I found that significantly more epidemic VEEV bound to and infected mosquito midguts compared to the enzootic strain. The dissemination from the midgut of an epidemic VEEV strain was compared to that of an enzootic strain. Following initial infection, the epidemic strain was pantropic in tissues of the mosquito, including the salivary glands, whereas the enzootic strain did not infect the midgut efficiently and replicated only in muscles and nervous tissue upon dissemination. \r\nFollowing the infection of the mosquito salivary glands with an epidemic strain, the amount of VEEV transmitted was estimated. I hypothesized that the method of mosquito infection and saliva collection significantly affects estimates of the amount of virus transmitted and that differing infection routes affect the viremia and mortality of mice. Both the mosquito species and infection route used affected the amount of virus detected in the saliva. The amount of VEEV transmitted in vivo by mosquitoes during blood feeding was significantly less than in vitro transmission estimates and mosquito transmission had little or no effect on murine viremia or mortality compared to needle inoculations. These results have important implications for evaluating the vector competence of Ae. taeniorhynchus and other VEEV vectors, for designing pathogenesis experiments, and for modeling transmission in nature.\r\n

vector, arbovirus, alphavirus