Respiratory Syncytial Virus Infection is Inhibited by Interferon-Induced Transmembrane Proteins----中国科学院微生物研究所

科研成果

论文题目:	Respiratory Syncytial Virus Infection is Inhibited by Interferon-Induced Transmembrane Proteins
作者:	Zhang Wei, Zhang Lei, Zan Yanlu, Du Ning, Yang Yang, Tien Po*
联系作者:	Tien Po*
刊物名称:	J Gen Virol
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年份:	2014
影响因子:	3.501
论文下载:	http://vir.sgmjournals.org/content/early/2014/09/16/vir.0.066555-0.long
摘要:	The interferon (IFN) immune system plays an essential role in protecting the host against most viral infections. In order to explore the interactions between the IFN pathway and Respiratory syncytial virus (RSV) infection, and to identify potential IFN-stimulated genes (ISGs) that may be involved in suppressing the replication of RSV, we utilized an IFN pathway-specific microarray to study the effects of RSV infection on the IFN pathway in HeLa cells. We showed that RSV infection enhanced the expression of a series of ISGs, including oligoadenylate synthetase 2 (OAS2), interferon-induced transmembrane protein 1 (IFITM1) and myxovirus-resistance 2 (Mx2). Our results also showed that the IFITM proteins potently inhibited RSV infection mainly by interfering with both virus entry and the subsequent replication steps, but not the attachment process. The anti-viral effect of IFITM3 protein was not affected by ubiquitination modification. Furthermore, knocking down the endogenous and IFN-induced expressions of IFITM1 and IFITM3 proteins facilitated RSV infection. Expression of the IFITM proteins was found to delay the phosphorylation of interferon regulatory factor-3 (IRF3) through interfering with the detection of viral RNA by the melanoma differentiation-associated gene 5 (MDA5) and the retinoic acid-inducible gene I (RIG-I). These results demonstrated that the restriction of RSV infection by the IFITM proteins was achieved through the inhibition of virus entry and replication, and they provide further insight for exploring the mechanism of IFITM proteins-mediated virus restriction.