Genotypic and phenotypic diversity of rabies virus variants involved in human rabies: implications for postexposure prophylaxis.
OBJECTIVE
Rabies virus variants associated with silver-haired bats (SHBRV) are responsible for most recent human rabies cases in the United States, which are not associated with a history of exposure. We compared their genotype and phenotype with those of dog rabies virus (DRV) variants, the classic cause of rabies in humans, to determine whether differences in these strains might have ramifications for therapeutic intervention, particularly vaccination.


METHODS
Eleven silver-haired bat and 8 dog rabies virus isolates were characterized by sequencing the glycoprotein gene, by assessing their ability to replicate in neuronal versus nonneuronal cultures at optimal and suboptimal temperatures, by assessing their pathogenicity in mice, and by determining the resistance of these viruses to therapeutic immunization with commercial vaccines.


RESULTS
SHBRV isolates were less genetically diverse, less neuronal cell specific, more temperature sensitive, but as pathogenic, on average, as DRV isolates. Immune protection was equivalent for SHBRV and DRV strains of similar pathogenicity.


CONCLUSIONS
SHBRV strains have unique characteristics that may explain their exceptional association with human rabies but have little bearing on their lethality in mice. The pathogenicity of a particular virus, rather than its antigenic makeup, determines the outcome of immunization.
Dietzschold
B
B
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Morimoto
K
K
Hooper
D C
DC
Smith
J S
JS
Rupprecht
C E
CE
Koprowski
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002685:Chiroptera; D004285:Dogs; D019204:GTP-Binding Proteins / Q000737:chemistry; D005838:Genotype; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D011818:Rabies / Q000517:prevention & control* / Q000821:virology; D012209:Rhabdoviridae / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014611:Vaccination; D014764:Viral Proteins / Q000737:chemistry; D014765:Viral Vaccines / Q000008:administration & dosage
D014764:Viral Proteins; D014765:Viral Vaccines; D019204:GTP-Binding Proteins