Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

• Published in: Virology (New York, N.Y.) N.Y.), 2016-01, Vol.487, p.230-241
• Main Authors: Akhrymuk, Ivan, Frolov, Ilya, Frolova, Elena I
• Format: Article
• Language: English
• Subjects: 3T3 Cells; 60 APPLIED LIFE SCIENCES; Alphavirus - genetics; Alphavirus - growth & development; Alphavirus - immunology; Alphaviruses; Animals; Cell Line; CONCENTRATION RATIO; Cricetinae; DEAD Box Protein 58; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DISEASE VECTORS; Gene Knock-In Techniques; Gene Knockdown Techniques; IMMUNITY; Immunity, Innate - immunology; IN VITRO; IN VIVO; Infectious Disease; Innate immunity; INTERFERON; Interferon-beta - immunology; Interferon-Induced Helicase, IFIH1; MDA5; Mice; MOSQUITOES; PATTERN RECOGNITION; Pattern recognition receptors; PUBLIC HEALTH; RECEPTORS; Receptors, Pattern Recognition - immunology; RIG-I; RNA; Type I interferon; VERTEBRATES; Virus Replication; VIRUSES; Virus–host interactions
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.09.023

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.