The RNase L inhibitor (RLI) is induced by double-stranded RNA

The (2-5A)-RNase L pathway is an important component of interferon (IFN) ac tion. Its central role in the antiviral effect of IFN against Picornavirida e has been clearly demonstrated. We have characterized and cloned a new com ponent of this pathway, the RNase L inhibitor (RLI). RLI is a cellular prot ein whose mRNA is not regulated by IFN but is induced by viruses, such as e ncephalomyocarditis virus (EMCV). RLI inhibits RNase L during the time cour se of EMCV infection, and overexpression of RLI in HeLa cells partially rev erses the antiviral action of IFN against EMCV. The replicative complexes o f several viruses consist of double-stranded RNA structures. These dsRNAs c ould activate gene transcription as demonstrated for IFNs and could be resp onsible for RLI induction. We describe the increased expression of RLI mRNA and RLI protein induced by synthetic dsRNAs, such as poly(I):poly(C). This induction gives rise to an inhibition of the 2-5A-binding activity of RNas e L. The inhibition of RNase L activity is transcient, probably due to the rapid turnover of RLI protein.