在一项新的研究中，来自美国北卡罗来纳大学（UNC）医学院和桑福德-伯纳姆-普利贝斯医学探索研究所（Sanford Burnham Prebys Medical Discovery Institute, SBP）的研究人员鉴定出人（宿主）蛋白削弱人体对HIV和其他病毒作出的免疫反应。这一发现对改变HIV抗病毒疗法、构建有效的病毒疫苗和开发治疗癌症的新方法产生重要影响。相关研究结果发表在2016年4月13日那期Cell Host & Microbe期刊上，论文标题为“NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses”。
作者: ipsvirus 时间: 2016-4-20 10:07 NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses
Haitao Guo1, 13, Renate König2, 3, 13, Meng Deng1, 4, Maximilian Riess3, Jinyao Mo5, Lu Zhang1, Alex Petrucelli1, Sunnie M. Yoh2, Brice Barefoot7, Melissa Samo7, Gregory D. Sempowski7, Aiping Zhang8, Anamaris M. Colberg-Poley8, 9, Hui Feng1, Stanley M. Lemon1, 5, 10, Yong Liu1, 11, Yanping Zhang1, 11, Haitao Wen1, Zhigang Zhang1, Blossom Damania1, 10, Li-Chung Tsao1, Qi Wang1, Lishan Su1, 10, Joseph A. Duncan1, 5, 6, Sumit K. Chanda2, , , Jenny P.-Y. Ting1, 10, 12, ,
Highlights
•NLRX1 inhibits HIV-1 cDNA-induced innate immune response and enhances HIV-1 infection
•NLRX1 interacts with the DNA-sensing adaptor STING to disrupt STING-TBK1 signaling
•STING deficiency abrogates the enhancement of HIV-1 infection by NLRX1
•Nlrx1−/− mice show enhanced innate immunity and are more resistant to DNA viruses
Summary
Understanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1−/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses.
