Aerosol infection of cynomolgus macaques with enzootic strains of Venezuelan equine encephalitis viruses

Because Venezuelan equine encephalitis viruses (VEEVs) are infectious by aerosol, they are considered to be a biological-weapons threat. Nonhuman-primate models are needed to evaluate the efficacy of candidate vaccines. In the present study, cynomolgus macaques, after aerosol exposure to either VEEV-IE or VEEV-IIIA, developed fever, viremia, and lym-phopenia; the severity of the fever response, viremia, and lymphopenia correlated with the inhaled dose of VEEV. Of the 10 macaques in our study, 7 developed clinical signs indicative of encephalitis, including loss of balance and hy-pothermia. In the macaque, the enzootic strains used are infectious by aerosol and lead to disease, including clinical encephalitis. Venezuelan equine encephalitis viruses (VEEVs) are a group (family, Togaviridae; genus, Alphavirus) of small, related, pos-itive-stranded RNA viruses endemic to Central and South America. Six subtypes containing 9 varieties of VEEVs have been identified by serology; most of them are enzootic and are thought to circulate through rodent hosts by a mosquito vector [1]. Widespread equine and human outbreaks have occasionally emerged, most of which have been caused by the IA/B and IC strains [2]. Isolated cases of human and equine disease caused by infection with the enzootic strains of other varieties and subtypes have also been reported [3, 4]. Typical human symp