Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein
Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein
复制标题
甲型流感病毒诱导的 ISG20 表达通过与核蛋白相互作用抑制病毒复制
DOI：
10.1007/s11262-016-1366-2
复制
发表时间：
2016-12-01
期刊：
影响因子：
1.6
通讯作者：
He, Hongxuan
中科院分区：
文献类型：
--
作者：
Qu, Hongren;Li, Jing;He, Hongxuan
甲型流感病毒（IAV）是一种重要的病原体，具有广泛的宿主，并对人类和几种动物物种的健康构成威胁。IAV感染可诱导宿主体内多种基因的转录。在本研究中，我们首次证明了三种不同的H1N1 IAV毒株诱导IFN刺激基因ISG20的表达。我们确定了ISG20对IAV的抗病毒活性，因为ISG20抑制病毒蛋白表达并降低子代病毒滴度，这取决于其核酸外切酶活性。为了阐明ISG20的详细机制，我们进一步证明了ISG20损害聚合酶活性并抑制M1和NP基因的复制和转录水平。值得注意的是，我们确定了ISG20共定位和相互作用与NP在IAV感染，而核酸外切酶失活突变ISG20缺乏与NP的关联，表明ISG20抑制IAV复制通过与NP相互作用。总之，这些数据为ISG20的特异性抗病毒作用提供了详细的解释，并表明ISG20可能作为一种有希望的抗IAV的抗病毒候选药物。
Influenza A virus (IAV) is an important pathogen that has a wide range of hosts and represents a threat to the health of humans and several animal species. IAV infection can induce the transcription of many genes in the host. In the present study, we demonstrated for the first time that three different strains of H1N1 IAV induce the expression of an IFN-stimulated gene, ISG20. We determined the antiviral activity of ISG20 against IAV because ISG20 inhibited viral protein expression and reduced the progeny viral titer dependent upon its exonuclease activity. To elucidate the detailed mechanism of ISG20, we further demonstrated that ISG20 impairs the polymerase activity and inhibits both the replication and transcription levels of the M1 and NP genes. Notably, we identified that ISG20 colocalizes and interacts with NP during IAV infection, while exonuclease-inactive mutant ISG20 lacked association with NP, indicating that ISG20 inhibits IAV replication by interacting with NP. Together, these data provide a detailed explanation for the specific antiviral action of ISG20 and suggest that ISG20 may act as a promising antiviral drug candidate against IAV.