Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon

Xin Li, Meng Deng, Alex S. Petrucelli, Cheng Zhu, Jinyao Mo, Lu Zhang, Jason W. Tam, Pablo Ariel, Baoyu Zhao, Song Zhang, Hengming Ke, Pingwei Li, Nikolay V. Dokholyan, Joseph A. Duncan, Jenny P.Y. Ting

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition. NLRC3 is a negative regulator that attenuates type I interferon (IFN-I) response by sequestering and attenuating stimulator of interferon genes (STING) activation. Here, we report that NLRC3 binds viral DNA and other nucleic acids through its LRR domain. DNA binding to NLRC3 increases its ATPase activity, and ATP-binding by NLRC3 diminishes its interaction with STING, thus licensing an IFN-I response. This work uncovers a mechanism wherein viral nucleic acid binding releases an inhibitory innate receptor from its target.

Original languageEnglish (US)
Pages (from-to)591-599.e6
JournalImmunity
Volume50
Issue number3
DOIs
StatePublished - Mar 19 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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