Cytosolic infection with DNA viruses triggers innate immune responses via the STING adaptor pathway, which activates the kinase TBK1 and transcription factors IRF3 and NF-κB to produce type I interferons. In Cell Host & Microbe, Guo et al. report that the Nod-like receptor NLRX1 is a negative regulator of STING. NLRX1-deficient cells express more type I interferons after infection with the retrovirus HIV-1 or treatment with cyclic GAMP or cyclic di-GMP, which activate STING-dependent responses. NLRX1 seems to block the interaction of STING with TBK1, which prevents downstream activation. Given that NLRX1 is localized to mitochondrial membranes, whereas STING is tethered to the endoplasmic reticulum, the kinetics of their interaction and how these proteins come into promixity still need to be determined. Nevertheless, interfering with NLRX1's activity might enhance anti-viral responses, including those directed against HIV-1.

Cell Host Microbe 19, 515–528 (2016)