Immunological findings of West Caucasian bat virus in an accidental host

The Lyssavirus genus includes seventeen neurotropic viral species which are able to cause rabies, an acute and almost invariably fatal encephalomyelitis of mammals. Rabies virus (RABV), the genus prototype, is a multi-host pathogen that undergoes multiple events of host-switching, thus occupying several geographical and ecological niches. In contrast, non-RABV lyssaviruses are mainly confined within a single natural host with rare spillover events never followed by adaptation to new accidental host species. In this scenario, unveiling the mechanisms underlying the host immune response against a virus is crucial to understand the dynamics of infection but also to predict the probability of colonization and adaptation to a new target species. Presently, the host response to lyssaviruses has only been partially explored, with the majority of data inferred from RABV infection, under the assumption that all members of the genus exhibit a similar behavior. Through our study we have investigated the immune response determined by the West Caucasian bat virus (WCBV). Indeed, WCBV has been recently associated with a spillover event to a domestic cat, raising concern about the risks for public health due to the circulation of the virus in its natural host. We selected the Syrian hamster as an animal model representative for an accidental host, and chose the intramuscular route in order to mimic the natural route of infection. In hamsters, WCBV was highly pathogenic, determining 100% lethality and mild encephalitis. In comparison with Duvenhage virus (DUVV) and RABV, we found that WCBV displayed an intermediate ability to promote cellular antiviral response, produce pro-inflammatory cytokines, recruit and activate lymphocytes in the hamsters’ central nervous system.