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Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1530-5. doi: 10.1073/pnas.0811029106. Epub 2009 Jan 21.

Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria.

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National Key Laboratory of Protein Engineering and Plant Gene Engineering, College of Life Sciences, Peking University, Beijing, China.


gC1qR is one of the C1q receptors implicated in the regulation of innate and adaptive immunity. We found that gC1qR inhibits RIG-I and MDA5-dependent antiviral signaling. Double stranded RNA and virus trigger the translocation of gC1qR to the mitochondrial outer membrane leading to the interaction of gC1qR with the RIG-I and MDA5 adaptor, VISA/MAVS/IPS-1/Cardif. The interaction of gC1qR with VISA/MAVS/IPS-1/Cardif at mitochondria results in the disruption of RIG-I and MDA5 signaling and the promotion of virus replication. Knockdown of endogenous gC1qR enhances RIG-I-dependent antiviral signaling, and augments the inhibition of virus proliferation. Therefore, gC1qR is a physiological inhibitor of the RIG-I and MDA5-mediated antiviral signaling pathway. These data uncover a new viral mechanism used to negatively control antiviral signaling in host cells.

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