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

ABSTRACT: The RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) trigger inflammatory and antiviral responses by sensing non-self RNA molecules produced during viral replication. LGP2 regulation of RIG-I and MDA5-dependant type-I interferon signaling is a matter of controversy. Here we show that LGP2 interacts with different components of the RNA silencing machinery. Particularly, we identified a direct protein-protein interaction between LGP2 and interferon-inducible double-stranded RNA-dependent protein kinase activator A (PACT). The LGP2-PACT interaction is mediated by the regulatory C-terminal domain of LGP2 and is necessary for inhibiting the RIG-I- and amplifying the MDA5-responses. We describe a point mutation within LGP2 that disrupts LGP2-PACT interaction and leads to the loss of LGP2 regulatory activity over RIG-I and MDA5. These results provide a model in which PACT-LGP2 interaction regulates RIG-I and MDA5 inflammatory response and allows cellular RNA silencing machinery to coordinate the innate immune response.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mengo Virus

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Thibaut LEGER  

LAB HEAD: Dr. Anastassia Komarova

PROVIDER: PXD013191 | Pride | 2019-10-02

REPOSITORIES: Pride