Genotypic and phenotypic diversity of rabies virus variants involved in human rabies: Implications for postexposure prophylaxis

Objectives: Rabies virus variants associated with silver-haired bats (SHBRV ) are responsible for most recent human rabies cases in the United States. which are nor associated with a history of exposure. We compared their geno type and phenotype with those of dog rabies virus (DRV) variants, the class ic cause of rabies in humans, to determine whether differences in these str ains might have ramifications for therapeutic intervention, particularly va ccination. Methods: Eleven silver-haired bat and 8 dog rabies virus isolates were char acterized by sequencing the glycoprotein gene, by assessing their ability t o replicate in neuronal versus nonneuronal cultures at optimal and suboptim al temperatures, by assessing their pathogenicity in mice, and by determini ng the resistance of these viruses to therapeutic immunization with commerc ial vaccines. Results: SHURV isolates were less genetically diverse, less neuronal cell s pecific, more temperature sensitive. but as pathogenic, on average, as DRV isolates. Immune protection was equivalent fur SHBRV and DRV strains of sim ilar pathogenicity. Conclusions: SHBRV strains have unique characteristics that ma? explain the ir exceptional association with human rabies but have little bearing on the ir lethality in mice. The pathogenicity of a particular virus, rather than its antigenic makeup, determines the outcome of immunization.