Immunological findings of West Caucasian bat virus in an accidental host

The Lyssavirus genus includes seventeen viral species all neurotropic and able to determine rabies, an acute and almost invariably fatal encephalomyelitis of mammals. Lyssavirus rabies (RABV), the genus prototype, is a multi-host pathogen that undergoes multiple events of host-switching, thus occupying several geographical and ecological niches. On the opposite, 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 context, unveiling the molecular connections between a virus and the host immune response represents a key determinant to understand the infection dynamics and ultimately predict the likelihood for the colonization and adaptation of a new target species. Currently, host response against lyssaviruses has only partially been addressed with most data inferred from RABV infection, assuming all genus members perform the same. We have therefore investigated the immune response determined by the Lyssavirus caucasicus (WCBV). Indeed, WCBV has been recently associated with a spillover event to a domestic cat, raising concern about the public health risks due to the viral circulation in its natural host. We selected Syrian hamster as an animal model representative for an accidental host, and chose the intramuscular route in order to mimic the natural infection. In hamsters, WCBV was highly pathogenic, determining 100% lethality and mild encephalitis. In comparison with Duvenhage virus (DUVV) and RABV, we found that, unexpectedly, WCBV displayed an intermediate ability to promote cellular antiviral response, pro-inflammatory cytokines, and lymphocyte recruitment and activation in the hamsters' central nervous system (CNS).