NLRX1 is a regulator of mitochondrial antiviral immunity

Chris B. Moore, Daniel T. Bergstralh, Joseph A. Duncan, Yu Lei, Thomas E. Morrison, Albert G. Zimmermann, Mary A. Accavitti-Loper, Victoria J. Madden, Lijun Sun, Zhengmao Ye, John D. Lich, Mark T. Heise, Zhijian Chen, Jenny P Y Ting

Research output: Contribution to journalArticle

365 Citations (Scopus)

Abstract

The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-β promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.

Original languageEnglish (US)
Pages (from-to)573-577
Number of pages5
JournalNature
Volume451
Issue number7178
DOIs
StatePublished - Jan 31 2008

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Antiviral Agents
Immunity
Interferon Type I
Mitochondria
Viruses
RNA Viruses
Mitochondrial Membranes
Virus Diseases
Leucine
Nucleic Acids
Interferons
Nucleotides
Cytokines
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Moore, C. B., Bergstralh, D. T., Duncan, J. A., Lei, Y., Morrison, T. E., Zimmermann, A. G., ... Ting, J. P. Y. (2008). NLRX1 is a regulator of mitochondrial antiviral immunity. Nature, 451(7178), 573-577. https://doi.org/10.1038/nature06501

NLRX1 is a regulator of mitochondrial antiviral immunity. / Moore, Chris B.; Bergstralh, Daniel T.; Duncan, Joseph A.; Lei, Yu; Morrison, Thomas E.; Zimmermann, Albert G.; Accavitti-Loper, Mary A.; Madden, Victoria J.; Sun, Lijun; Ye, Zhengmao; Lich, John D.; Heise, Mark T.; Chen, Zhijian; Ting, Jenny P Y.

In: Nature, Vol. 451, No. 7178, 31.01.2008, p. 573-577.

Research output: Contribution to journalArticle

Moore, CB, Bergstralh, DT, Duncan, JA, Lei, Y, Morrison, TE, Zimmermann, AG, Accavitti-Loper, MA, Madden, VJ, Sun, L, Ye, Z, Lich, JD, Heise, MT, Chen, Z & Ting, JPY 2008, 'NLRX1 is a regulator of mitochondrial antiviral immunity', Nature, vol. 451, no. 7178, pp. 573-577. https://doi.org/10.1038/nature06501
Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG et al. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature. 2008 Jan 31;451(7178):573-577. https://doi.org/10.1038/nature06501
Moore, Chris B. ; Bergstralh, Daniel T. ; Duncan, Joseph A. ; Lei, Yu ; Morrison, Thomas E. ; Zimmermann, Albert G. ; Accavitti-Loper, Mary A. ; Madden, Victoria J. ; Sun, Lijun ; Ye, Zhengmao ; Lich, John D. ; Heise, Mark T. ; Chen, Zhijian ; Ting, Jenny P Y. / NLRX1 is a regulator of mitochondrial antiviral immunity. In: Nature. 2008 ; Vol. 451, No. 7178. pp. 573-577.
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