NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses

Haitao Guo, Renate König, Meng Deng, Maximilian Riess, Jinyao Mo, Lu Zhang, Alex Petrucelli, Sunnie M. Yoh, Brice Barefoot, Melissa Samo, Gregory D. Sempowski, Aiping Zhang, Anamaris M. Colberg-Poley, Hui Feng, Stanley M. Lemon, Yong Liu, Yanping Zhang, Haitao Wen, Zhigang Zhang, Blossom DamaniaLi Chung Tsao, Qi Wang, Lishan Su, Joseph A. Duncan, Sumit K. Chanda, Jenny P.Y. Ting

Research output: Contribution to journalArticle

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalCell Host and Microbe
Volume19
Issue number4
DOIs
StatePublished - Apr 13 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Guo, H., König, R., Deng, M., Riess, M., Mo, J., Zhang, L., Petrucelli, A., Yoh, S. M., Barefoot, B., Samo, M., Sempowski, G. D., Zhang, A., Colberg-Poley, A. M., Feng, H., Lemon, S. M., Liu, Y., Zhang, Y., Wen, H., Zhang, Z., ... Ting, J. P. Y. (2016). NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses. Cell Host and Microbe, 19(4), 515-528. https://doi.org/10.1016/j.chom.2016.03.001