title: Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode.
abstract: Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Akhrymuk
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA. Electronic address: evfrolova@UAB.edu.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Frolova
mesh_terms: D016475:3T3 Cells; D000524:Alphavirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D007113:Immunity, Innate / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000276:immunology*; D051379:Mice; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D014779:Virus Replication
chemical_list: D051192:Receptors, Pattern Recognition; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Alphaviruses; Innate immunity; MDA5; Pattern recognition receptors; RIG-I; Type I interferon; Virus–host interactions