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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Guo, H; König, R; Deng, M; Riess, M; Mo, J; Zhang, L; Petrucelli, A; Yoh, SM; Barefoot, B; Samo, M; Sempowski, GD; Zhang, A; Colberg-Poley, AM; Feng, H; Lemon, SM; Liu, Y; Zhang, Y; Wen, H; Zhang, Z; Damania, B; Tsao, L-C; Wang, Q; Su, L; Duncan, JA; Chanda, SK; Ting, JP-Y

Published Date

  • April 2016

Published In

Volume / Issue

  • 19 / 4

Start / End Page

  • 515 - 528

PubMed ID

  • 27078069

Pubmed Central ID

  • 27078069

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

International Standard Serial Number (ISSN)

  • 1931-3128

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2016.03.001

Language

  • eng