NLRX1 is a regulator of mitochondrial antiviral immunity.

NLRX1 is a regulator of mitochondrial antiviral immunity. Research Abstract Details 

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NLRX1 is a regulator of mitochondrial antiviral immunity. Abstract Text:

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,

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-beta 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.

NLRX1 is a regulator of mitochondrial antiviral immunity. Publishing Authors By Initials

CB Moore,DT Bergstralh,JA Duncan,Y Lei,TE Morrison,AG Zimmermann,MA Accavitti-Loper,VJ Madden,L Sun,Z Ye,JD Lich,MT Heise,Z Chen,JP Ting,

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NLRX1 is a regulator of mitochondrial antiviral immunity. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature

VOLUME: 451

Page Numbers: 573-7

Journal Abbreviation: Nature

ISSN: 1476-4687

DAY: 16

MONTH: 01

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 410462

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Grant and Affiliation Information for NLRX1 is a regulator of mitochondrial antiviral immunity.

AFFILIATION: Department of Microbiology-Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Country: England

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MEDLINETA: Nature

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