Cyclo(Phe-Pro) (Cyclo(phenylalanylprolyl)), a Vibrio vulnificus quorum-sensing molecule, inhibits retinoic acid-inducible gene-I (RIG-I) polyubiquitination, through its specific interaction with RIG-I, to blunt IRF-3 activation and type-I IFN production. Cyclo(Phe-Pro) (Cyclo(phenylalanylprolyl)) enhances susceptibility to hepatitis C virus (HCV), as well as Sendai and influenza viruses.