Understanding host responses to equine encephalitis virus infection: implications for therapeutic development

Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne New World alphaviruses that cause encephalitis in equids and humans. These viruses can cause severe disease and death, as well as long-term severe neurological symptoms in survivors. Despite the pathogenesis and weaponization of these viruses, there are no approved therapeutics for treating infection.In this review, we describe the molecular pathogenesis of these viruses, discuss host-pathogen interactions needed for viral replication, and highlight new avenues for drug development with a focus on host-targeted approaches.Current approaches have yielded some promising therapeutics, but additional emphasis should be placed on advanced development of existing small molecules and pursuit of pan-encephalitic alphavirus drugs. More research should be conducted on EEEV and WEEV, given their high lethality rates.