The pathogenesis of lyssavirus infection in bats is poorly known, making it difficult to determine the relevance of lyssavirus infection in bat populations, and to prevent and treat bat-origin lyssavirus infection in spillover... [ view full abstract ]
The pathogenesis of lyssavirus infection in bats is poorly known, making it difficult to determine the relevance of lyssavirus infection in bat populations, and to prevent and treat bat-origin lyssavirus infection in spillover hosts. Therefore, we developed an experimental infection model, using straw-colored fruit bats (Eidolon helvum, EH) and Lagos bat virus (LBV), an endemic lyssavirus in this species. First, we tested the ability of three LBV strains (from Nigeria, Senegal, and Ghana) to replicate in the brain. Each LBV strain was inoculated intracranially into three EH. Clinical signs differed per strain: weakness (Nigeria strain), hyperactivity (Senegal strain), or aggression (Ghana strain). Lyssavirus antigen was expressed in >25% of neurons (Nigeria and Senegal strains), compared to <25% of neurons (Ghana strain). Within neurons, lyssavirus antigen occurred as large (Nigeria strain) or small (Senegal and Ghana strains) intracytoplasmic granules. Regardless of LBV strain, the main lesion was lymphocytic meningoencephalitis. Second, we determined the lowest viral dose of Ghana strain (deemed preferable because it had the least cell passages) resulting in 100% productive infection. Each of five doses (neat [4.1 Ig] to 10-4) of Ghana strain was inoculated in the masseter muscle in four EH. The number of bats which displayed clinical signs, showed no clear correlation to dose: neat, 2/4 bats; 10-1, 2/4; 10-2, 4/4; 10-3, 2/4; 10-4, 1/4. Incubation period increased with virus dilution: neat, 8 days; 10-1, 7-18; 10-2, 10-17; 10-3, 7-12; 10-4, 61. The virus was neurotropic in all infected EH. Lyssavirus antigen was not expressed in salivary glands of any EH, but was in taste buds in 4/6 EH, suggesting viral excretion through taste buds. Together, these preliminary results indicate that intramuscular inoculation of a 10-2 dilution of Ghana LBV strain into EH comprises an appropriate model to study LBV pathogenesis in EH.