Mouse Functional Genetics, Institut Pasteur, Paris, France.
Virology. 2011 Aug 15;417(1):147-53. doi: 10.1016/j.virol.2011.05.018. Epub 2011 Jun 17.
Susceptibility of inbred strains to infection with West Nile virus (WNV) has been genetically associated with an arginine-to-a nonsense codon substitution at position 253 (R253X) in the predicted sequence of the murine 2',5'-oligoadenylate synthetase 1B (OAS1B) protein. We introduced by transgenesis the Oas1b cDNA from MBT/Pas mice carrying the R253 codon (Oas1b(MBT)) into BALB/c mice homozygous for the X253 allele (Oas1b(BALB/c)). Overexpression of Oas1b(MBT) mRNA in the brain of transgenic mice prior and in the time course of infection provided protection against the neuroinvasive WNV strain IS-98-ST1. A 200-fold induction of Oas1b(MBT) mRNA in the brain of congenic BALB/c mice homozygous for a MBT/Pas segment encompassing the Oas1b gene was also efficient in reducing both viral growth and mortality, whereas a 200-fold induction of Oas1b(BALB/c) mRNA was unable to prevent virally-induced encephalitis, confirming the critical role of the R253X mutation on Oas1b activity in live mice.
近交系对西尼罗河病毒（WNV）感染的易感性已被遗传关联到预测的鼠 2'，5'-寡聚腺苷酸合成酶 1B（OAS1B）蛋白序列中 253 位的精氨酸到无义密码子取代（R253X）。我们通过转基因将携带 R253 密码子的 MBT/Pas 小鼠的 Oas1b cDNA（Oas1b（MBT））引入 X253 等位基因纯合的 BALB/c 小鼠（Oas1b（BALB/c））。在感染前和感染过程中，转基因小鼠大脑中 Oas1b（MBT）mRNA 的过度表达为神经侵袭性 WNV 株 IS-98-ST1 提供了保护。在携带包含 Oas1b 基因的 MBT/Pas 片段的同基因 BALB/c 小鼠的大脑中，Oas1b（MBT）mRNA 的 200 倍诱导也能有效降低病毒的生长和死亡率，而 Oas1b（BALB/c）mRNA 的 200 倍诱导则不能防止病毒诱导的脑炎，这证实了 R253X 突变对活小鼠中 Oas1b 活性的关键作用。
