Multigenic relation to the attenuation of rabies virus
Multigenic relation to the attenuation of rabies virus
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DOI：
10.1111/j.1348-0421.2006.tb03767.x
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发表时间：
2006-01-01
影响因子：
2.6
通讯作者：
Minamoto, N
中科院分区：
文献类型：
--
作者：
Yamada, K;Ito, N;Minamoto, N
狂犬病毒西原株在成年小鼠脑内接种后可致死性感染。另一方面，来自Nishigahara菌株的RC-HL菌株不会在成年小鼠中引起致命感染。我们先前证明了嵌合病毒R(G)在RC-HL基因组背景中具有来自Nishigahara株的G基因开放阅读框（G- orf），具有毒性。反过来，为了证明RC-HL株的G基因与减毒表型有关，我们建立了Nishigahara株的反向遗传系统，在Nishigahara基因组背景下，用RC-HL的G- orf生成了嵌合病毒Ni(G)。与我们的预测相反，Ni(G)在脑内接种后杀死成年小鼠，并出现类似西原菌株感染的神经病变症状。因此，RC-HL株的G-ORF不是减毒表型的唯一决定因素。在进一步的研究中，我们检查了其他基因，包括N， P， M和L基因，并产生了嵌合病毒。我们发现，与来自RC-HL的单个基因嵌合的病毒没有被减毒，而与来自RC-HL的G-ORF和至少一个其他ORF的嵌合病毒被减毒。综上所述，从Nishigahara到RC-HL的衰减是多基因的。
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.