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Multigenic Relation to the Attenuation of Rabies Virus
Author(s) -
Yamada Kentaro,
Ito Naoto,
TakayamaIto Mutsuyo,
Sugiyama Makoto,
Minamoto Nobuyuki
Publication year - 2006
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2006.tb03767.x
Subject(s) - biology , virology , rabies virus , virus , gene , strain (injury) , open reading frame , attenuated vaccine , virulence , phenotype , genome , neurotropic virus , genetics , peptide sequence , anatomy
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.