Abstract:
Attenuation of rabies virus can be achieved by passaging virus into non-neuronal cells or by modification of genetic element(s). Following serial passages of Thai canine street rabies virus, QS-05, into BHK-21 cells, gave rise to highly pathogenic virus. At seventh passage, QS-BHK-P7 virus was able to cause lethality in adult mice by peripheral intramuscular and intracerebral (IC) challenges whereas its parental isolate could only kill by IC route. Comparison of whole genome sequences revealed that there were three missense mutations, two were located in ectodomain region of glycoprotein (G) gene (non-neuronal marker S23R and H424P at non-PDZ or pathogenic/immunogenic determinant sites) and the other (I1711V) in polymerase (L) gene. Another point mutation was at the seventh adenine residue of the poly (A) signal residing between the phospho (P) and matrix (M) protein genes. Roles of such mutation in L and intergenic P-M region remain to be elucidated.
