title: Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys.
abstract: Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to blunt-ended (5' ppp)dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes. We examined the ability of various dsRNAs to activate the RIG-I ATPase (presumably a measure of helicase translocation on dsRNA) relative to their ability to induce IFN. We found that there is no simple relationship between these two properties, as if RIG-I can translocate on short dsRNAs without inducing IFN. Moreover, we found that (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide can in fact competitively inhibit the ability of blunt-ended (5' ppp)dsRNAs to induce IFN when co-transfected into cells and that this inhibition is strongly dependent on the presence of the 5' ppp. In contrast, (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide does not inhibit poly(I-C)-induced IFN activation, which is independent of the presence of a 5' ppp group.
authors.affiliation: Department of Microbiology and Molecular Medicine, University of Geneva School of Medicine, CMU, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Marq
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hausmann
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veillard
authors.forename: Daniel
authors.initials: D
authors.lastname: Kolakofsky
authors.forename: Dominique
authors.initials: D
authors.lastname: Garcin
mesh_terms: D018050:Arenavirus / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D016679:Genome, Viral / Q000502:physiology*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic
chemical_list: C551867:5'PPP-RNA; D007369:Interferon Inducers; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D007372:Interferons; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C