Research ArticleImmunology

LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses

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Science Signaling  01 Oct 2019:
Vol. 12, Issue 601, eaar3993
DOI: 10.1126/scisignal.aar3993

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An antiviral PACT

The RIG-I–like receptors (RLRs) RIG-I and MDA5 sense cytosolic viral RNAs during infection and activate signaling pathways that culminate in the production of type I interferons (IFNs) and proinflammatory cytokines as part of the antiviral immune response. LGP2, another member of the RLR family, inhibits RIG-I–mediated responses while enhancing MDA5 signaling. Sanchez David et al. found that this differential effect of LGP2 depended on its binding to PACT, a cofactor of DICER in the processing of microRNAs. Mutation of a residue in LGP2 required for the LGP2-PACT interaction resulted in loss of the regulatory effect of LGP2 over the other RLRs. Together, these data provide evidence of a connection between the RNA-silencing machinery and the innate immune response.

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