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 Dokholyan, Joseph A. Duncan, Jenny P.Y. Ting

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Fingerprint

Interferon alpha-beta Receptor
Viral DNA
Nucleic Acids
Interferons
Interferon Type I
Licensure
Innate Immunity
Leucine
Transcriptional Activation
Genes
Adenosine Triphosphatases
Adenosine Triphosphate
Ligands
DNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Li, Xin ; Deng, Meng ; Petrucelli, Alex S. ; Zhu, Cheng ; Mo, Jinyao ; Zhang, Lu ; Tam, Jason W. ; Ariel, Pablo ; Zhao, Baoyu ; Zhang, Song ; Ke, Hengming ; Li, Pingwei ; Dokholyan, Nikolay ; Duncan, Joseph A. ; Ting, Jenny P.Y. / Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon. In: Immunity. 2019 ; Vol. 50, No. 3. pp. 591-599.e6.
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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.",
author = "Xin Li and Meng Deng and Petrucelli, {Alex S.} and Cheng Zhu and Jinyao Mo and Lu Zhang and Tam, {Jason W.} and Pablo Ariel and Baoyu Zhao and Song Zhang and Hengming Ke and Pingwei Li and Nikolay Dokholyan and Duncan, {Joseph A.} and Ting, {Jenny P.Y.}",
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Li, X, Deng, M, Petrucelli, AS, Zhu, C, Mo, J, Zhang, L, Tam, JW, Ariel, P, Zhao, B, Zhang, S, Ke, H, Li, P, Dokholyan, N, Duncan, JA & Ting, JPY 2019, 'Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon', Immunity, vol. 50, no. 3, pp. 591-599.e6. https://doi.org/10.1016/j.immuni.2019.02.009

Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon. / Li, Xin; Deng, Meng; Petrucelli, Alex S.; Zhu, Cheng; Mo, Jinyao; Zhang, Lu; Tam, Jason W.; Ariel, Pablo; Zhao, Baoyu; Zhang, Song; Ke, Hengming; Li, Pingwei; Dokholyan, Nikolay; Duncan, Joseph A.; Ting, Jenny P.Y.

In: Immunity, Vol. 50, No. 3, 19.03.2019, p. 591-599.e6.

Research output: Contribution to journalArticle

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AU - Li, Xin

AU - Deng, Meng

AU - Petrucelli, Alex S.

AU - Zhu, Cheng

AU - Mo, Jinyao

AU - Zhang, Lu

AU - Tam, Jason W.

AU - Ariel, Pablo

AU - Zhao, Baoyu

AU - Zhang, Song

AU - Ke, Hengming

AU - Li, Pingwei

AU - Dokholyan, Nikolay

AU - Duncan, Joseph A.

AU - Ting, Jenny P.Y.

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