日本脑炎病毒 NS1' 蛋白拮抗干扰素 β 的产生。
Japanese Encephalitis Virus NS1' Protein Antagonizes Interferon Beta Production.
机构信息
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
出版信息
Virol Sin. 2018 Dec;33(6):515-523. doi: 10.1007/s12250-018-0067-5. Epub 2018 Dec 12.
Japanese encephalitis virus (JEV) is a mosquito-borne virus and the major cause of viral encephalitis in Asia. NS1', a 52-amino acid C-terminal extension of NS1, is generated with a -1 programmed ribosomal frameshift and is only present in members of the Japanese encephalitis serogroup of flaviviruses. Previous studies demonstrated that NS1' plays a vital role in virulence, but the mechanism is unclear. In this study, an NS1' defected (rG66A) virus was generated. We found that rG66A virus was less virulent than its parent virus (pSA14) in wild-type mice. However, similar mortality caused by the two viruses was observed in an IFNAR knockout mouse model. Moreover, we found that rG66A virus induced a greater type I interferon (IFN) response than that by pSA14, and JEV NS1' significantly inhibited the production of IFN-β and IFN-stimulated genes. Taken together, our results reveal that NS1' plays a vital role in blocking type I IFN production to help JEV evade antiviral immunity and benefit viral replication.
日本脑炎病毒（JEV）是一种通过蚊子传播的病毒，也是亚洲病毒性脑炎的主要病因。NS1'是 NS1 的 52 个氨基酸 C 末端延伸，通过 -1 程序性核糖体移码产生，仅存在于黄病毒属的日本脑炎血清群成员中。先前的研究表明，NS1'在毒力方面发挥着重要作用，但具体机制尚不清楚。本研究生成了一个 NS1'缺陷（rG66A）病毒。我们发现 rG66A 病毒在野生型小鼠中的毒力比其亲本病毒（pSA14）低。然而，在 IFNAR 敲除小鼠模型中，两种病毒引起的死亡率相似。此外，我们发现 rG66A 病毒诱导的 I 型干扰素（IFN）反应大于 pSA14，而 JEV NS1' 显著抑制 IFN-β 和 IFN 刺激基因的产生。总之，我们的结果表明 NS1' 在阻断 I 型 IFN 产生方面发挥着重要作用，有助于 JEV 逃避抗病毒免疫并有利于病毒复制。
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