Hwang Sung-Woo, Kim DongIk, Jung Jae U, Lee Hye-Ra
Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Zikha Neurogenic Institute, 1501 San Pablo Street, Los Angeles, CA 90089, USA.
Biochem Biophys Res Commun. 2017 May 6;486(3):700-705. doi: 10.1016/j.bbrc.2017.03.101. Epub 2017 Mar 22.
Before an infection can be completely established, the host immediately turns on the innate immune system through activating the interferon (IFN)-mediated antiviral pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes a unique antagonistic mechanism of type I IFN-mediated host antiviral immunity by incorporating four viral interferon regulatory factors (vIRF1-4). Herein, we characterized novel immune evasion strategies of vIRF4 to inhibit the IRF7-mediated IFN-α production. KSHV vIRF4 specifically interacts with IRF7, resulting in inhibition of IRF7 dimerization and ultimately suppresses IRF7-mediated activation of type I IFN. These results suggest that each of the KSHV vIRFs, including vIRF4, subvert IFN-mediated anti-viral response via different mechanisms. Therefore, it is indicated that KSHV vIRFs are indeed a crucial immunomodulatory component of their life cycles.
在感染完全确立之前，宿主会通过激活干扰素（IFN）介导的抗病毒途径立即启动固有免疫系统。卡波西肉瘤相关疱疹病毒（KSHV）通过整合四种病毒干扰素调节因子（vIRF1 - 4），利用一种独特的拮抗机制来对抗I型IFN介导的宿主抗病毒免疫。在此，我们对vIRF4抑制IRF7介导的IFN -α产生的新型免疫逃逸策略进行了表征。KSHV vIRF4特异性地与IRF7相互作用，导致IRF7二聚化受到抑制，并最终抑制IRF7介导的I型IFN激活。这些结果表明，包括vIRF4在内的每个KSHV vIRF都通过不同机制破坏IFN介导的抗病毒反应。因此，表明KSHV vIRF确实是其生命周期中关键的免疫调节成分。
