Multigenic relation to the attenuation of rabies virus.
Rabies virus Nishigahara strain causes lethal infection in adult mice after intracerebral inoculation. On the other hand, the RC-HL strain, derived from the Nishigahara strain, does not cause lethal infection in adult mice. We previously demonstrated that a chimeric virus, R(G), with the open reading frame of the G gene (G-ORF) from the Nishigahara strain in the background of the RC-HL genome, is virulent. Reversely, in order to demonstrate that the G gene of the RC-HL strain is related to the attenuated phenotype, we established a reverse genetics system of the Nishigahara strain and generated a chimeric virus, Ni(G), with the G-ORF from RC-HL in the background of the Nishigahara genome. Contrary to our prediction, Ni(G) killed adult mice after intracerebral inoculation with neuropathic symptoms like those of Nishigahara strain infection. Therefore, the G-ORF of the RC-HL strain is not the sole determinant of the attenuated phenotype. In additional investigation, we examined other genes, including N, P, M and L genes, and generated chimeric viruses exhaustively. We found that chimeric viruses with a single gene from the RC-HL were not attenuated and that chimeric viruses with the G-ORF and at least one other ORF from the RC-HL were attenuated. In conclusion, attenuation from the Nishigahara to RC-HL strain is multigenic.
Yamada
Kentaro
K
The United Graduate School of Veterinary Sciences, Division of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu, Gifu 501-1193, Japan.
Ito
Naoto
N
Takayama-Ito
Mutsuyo
M
Sugiyama
Makoto
M
Minamoto
Nobuyuki
N
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001835:Body Weight; D002460:Cell Line; D006224:Cricetinae; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D051379:Mice; D018832:Molecular Chaperones; D019251:Nucleocapsid / Q000235:genetics; D019590:Nucleocapsid Proteins; D010750:Phosphoproteins / Q000235:genetics; D011818:Rabies / Q000821:virology*; D011820:Rabies virus / Q000235:genetics* / Q000472:pathogenicity*; D011995:Recombination, Genetic; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics*
D000956:Antigens, Viral; D006023:Glycoproteins; D018832:Molecular Chaperones; D019590:Nucleocapsid Proteins; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C064951:glycoprotein G, Rabies virus; C099601:nucleocapsid protein, Rabies virus; C097625:L protein, Rabies virus; D012321:DNA-Directed RNA Polymerases