title: Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I-like receptors: hide, mask, hit.
abstract: Double-stranded RNA (dsRNA) is synthesized during the course of infection by RNA viruses as a byproduct of replication and transcription and acts as a potent trigger of the host innate antiviral response. In the cytoplasm of the infected cell, recognition of the presence of viral dsRNA as a signature of "non-self" nucleic acid is carried out by RIG-I-like receptors (RLRs), a set of dedicated helicases whose activation leads to the production of type I interferon α/β (IFN-α/β). To overcome the innate antiviral response, RNA viruses encode suppressors of IFN-α/β induction, which block RLRs recognition of dsRNA by means of different mechanisms that can be categorized into: (i) dsRNA binding and/or shielding ("hide"), (ii) dsRNA termini processing ("mask") and (iii) direct interaction with components of the RLRs pathway ("hit"). In light of recent functional, biochemical and structural findings, we review the inhibition mechanisms of RLRs recognition of dsRNA displayed by a number of highly pathogenic RNA viruses with different disease phenotypes such as haemorrhagic fever (Ebola, Marburg, Lassa fever, Lujo, Machupo, Junin, Guanarito, Crimean-Congo, Rift Valley fever, dengue), severe respiratory disease (influenza, SARS, Hendra, Hantaan, Sin Nombre, Andes) and encephalitis (Nipah, West Nile).
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella di Monserrato, SS554, 09042 Monserrato (Cagliari), Italy. Electronic address: lucazinzula@unica.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Zinzula
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D020365:RNA Helicases / Q000502:physiology*; D012327:RNA Virus Infections / Q000276:immunology / Q000821:virology*; D012328:RNA Viruses / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D014774:Virulence; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases
keywords: Innate immune system evasion; Interferon alpha/beta; LGP2; MDA5; RIG-I; Viral dsRNA detection