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An Antiviral PACT

By 3rd October 2019 October 8th, 2019 No Comments

Researchers at the Institut Pasteur in Paris led by Frédéric Tangy and Anastassia Komarova have identified a molecular mechanism that coordinates the activity of the cellular RNA-silencing machinery with antiviral responses. Cells sense infection by RNA viruses through the RIG-I–like receptors (RLRs) RIG-I and MDA5. These receptors, which are found in the cytosol of cells, stimulate innate immune responses, including the production of type I interferons (IFNs) and proinflammatory molecules, when they are activated by binding to viral RNAs. LGP2 is also a member of the RLR family, but it inhibits RIG-I–mediated antiviral responses and promotes MDA5-mediated antiviral responses.

The researchers, reporting their work in Science Signaling, found that this differential effect of LGP2 depended on its binding to PACT, a cofactor of DICER that functions in the processing of microRNAs. Mutation of an amino acid residue in LGP2 that is 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.

Read the research paper: LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses. R.Y. Sanchez David et al. Science Signaling 10.1126/scisignal.aar3993

Materials provided by the American Association for the Advancement of Science (AAAS).