title: Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection.
abstract: Rabies virus Nishigahara strain kills adult mice after intracerebral inoculation, whereas the derivative RC-HL strain does not. It has previously been reported by us that the R(G 242/255/268) strain, in which amino acids at positions 242, 255 and 268 on the G protein have been replaced by those from the Nishigahara strain in the genetic background of the RC-HL strain, kills adult mice.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 which 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 were compared. RC-HL infection spread less efficiently in the mouse brain than did R(G 242/255/268) infection. However, the apoptosis-inducing abilities of both viruses were almost identical, as shown by both in vitro and in vivo experiments. It was demonstrated that cell-to-cell spread of RC-HL strain was 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.
authors.affiliation: The United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Naoto
authors.initials: N
authors.lastname: Ito
authors.forename: Shouichiro
authors.initials: S
authors.lastname: Saito
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Masatani
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Atoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugiyama
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000821:virology; D002460:Cell Line; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011818:Rabies / Q000503:physiopathology / Q000821:virology*; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: D006023:Glycoproteins; D014759:Viral Envelope Proteins