Meyer Keith, Kwon Young-Chan, Liu Shuanghu, Hagedorn Curt H, Ray Ratna B, Ray Ranjit
Department of Internal Medicine, Saint Louis University.
Department of Medicinal Chemistry, College of Pharmacy, University of Utah.
Sci Rep. 2015 Mar 11;5:9012. doi: 10.1038/srep09012.
Viral entry requires co-operative interactions of several host cell factors. Interferon (IFN) and the IFN-stimulated genes (ISGs) play a central role in antiviral responses against hepatitis C virus (HCV) infection. We examined the effect of interferon-α inducible protein 6 (IFI6) against HCV infection in human hepatoma cells. HCV RNA level or infectious foci were inhibited significantly by ectopic expression of IFI6. IFI6 impaired CD81 co-localization with claudin-1 (CLDN1) upon HCV infection or CD81 cross-linking by specific antibody. Activation of epidermal growth factor receptor (EGFR), a co-factor involved in CD81/CLDN1 interactions, was reduced in IFI6 expressing cells in response to HCV infection or CD81 cross linking by antibody, but not by treatment with EGF. Taken together, the results from our study support a model where IFI6 inhibits HCV entry by impairing EGFR mediated CD81/CLDN1 interactions. This may be relevant to other virus entry processes employing EGFR.
病毒进入需要多种宿主细胞因子的协同相互作用。干扰素（IFN）和干扰素刺激基因（ISG）在针对丙型肝炎病毒（HCV）感染的抗病毒反应中起核心作用。我们研究了干扰素-α诱导蛋白6（IFI6）对人肝癌细胞中HCV感染的影响。IFI6的异位表达显著抑制了HCV RNA水平或感染灶。在HCV感染或通过特异性抗体进行CD81交联时，IFI6损害了CD81与紧密连接蛋白1（CLDN1）的共定位。在响应HCV感染或通过抗体进行CD81交联时，参与CD81/CLDN1相互作用的辅助因子表皮生长因子受体（EGFR）的激活在表达IFI6的细胞中降低，但用表皮生长因子（EGF）处理则未降低。综上所述，我们的研究结果支持一种模型，即IFI6通过损害EGFR介导的CD81/CLDN1相互作用来抑制HCV进入。这可能与采用EGFR的其他病毒进入过程相关。
