Susceptibility of sheep to European bat lyssavirus type-1 and -2 infection: a clinical pathogenesis study

European bat lyssaviruses (EBLVs) have been known to cross the species barrier from their native bat host to other terrestrial mammals. In this study, we have confirmed EBLV-1 and EBLV-2 susceptibility in sheep (Ovis ammon) following intracranial and peripheral (intramuscular) inoculation. Notably, mild clinical disease was observed in those exposed to virus via the intramuscular route. Following the intramuscular challenge, 75% of the animals infected with EBLV-1 and 100% of those that were challenged with EBLV-2 developed clinical signs of rabies and then recovered during the 94-day observation period. Disease pathogenesis also varied substantially between the two viruses. Infection with EBLV-1 resulted in peracute clinical signs, which are suggestive of motor neuron involvement. Antibody induction was observed and substantial inflammatrory infiltrate in the brain. In contrast, more antigen was detected in the EBLV-2-infected sheep brains but less inflammatory infiltrate and no virus neutralising antibody was evident. The latter involved a more protracted disease that was behaviour orientated. A high infectious dose was required to establish EBLV infection under experimental conditions (> or =5.0 logs/ml) but the infectious dose in field cases remains unknown. These data confirm that sheep are susceptible to infection with EBLV but that there is variability in pathogenesis including neuroinvasiveness that varies with the route of infection. This study suggests that inter-species animal-to-animal transmission of a bat variant of rabies virus to a terrestrial mammal host may be limited, and may not always result in fatal encephalitis.