Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection

Rabies virus Nishigahara strain kills adult mice after intracerebral inoculation, hereas the derivative RC-HL strain does not. It has previously been reported by us that the R(G 242/255/268) strain, in hich amino acids at positions 242, 255 and 268 on the G protein have been replaced by those from the Nishigahara strain in the genetic background of the RC-HL strain, kills adult mice. This indicates that these three amino acids of G protein are important for pathogenicity of the Nishigahara strain. In order to obtain insights into the mechanism by hich these amino acids affect pathogenicity, in this study spread of viral infection and apoptosis-inducing ability of the attenuated RC-HL strain and the virulent R(G 242/255/268) strain ere compared. RC-HL infection spread less efficiently in the mouse brain than didR(G242/255/268) infection.Hoever, the apoptosis-inducing abilities ofboth virusesere almost identical, as shon by both in vitro and in vivo experiments. It as demonstrated that cell-to-cell spread of RC-HL strain as less efficient than that of R(G 242/255/268) strain in mouse neuroblastoma cells. These results indicate that the three amino acid substitutions affect efficiency of cell-to-cell spread but not apoptosis-inducing ability, probably resulting in the distinct distributions of RC-HL and R(G 242/255/268) strain-infected cells in the mouse brain and, consequently, the different pathogenicities of these strains.