| Literature DB >> 27078069 |
Haitao Guo1, Renate König2,3, Meng Deng1,4, Maximilian Riess3, Jinyao Mo5, Lu Zhang1, Alex Petrucelli1, Sunnie M Yoh2, Brice Barefoot6, Melissa Samo6, Gregory D Sempowski6, Aiping Zhang7, Anamaris M Colberg-Poley7,8, Hui Feng1, Stanley M Lemon1,5,9, Yong Liu1,10, Yanping Zhang1,10, Haitao Wen1, Zhigang Zhang1, Blossom Damania1, Li-Chung Tsao1, Qi Wang1, Lishan Su1,9, Joseph A Duncan1,5,11, Sumit K Chanda2, Jenny P-Y Ting1,9,12.
Abstract
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.Entities:
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Year: 2016 PMID： 27078069 PMCID： PMC4833116 DOI： 10.1016/j.chom.2016.03.001
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023