title: Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus.
abstract: Type I interferons (IFNs) play a critical role in the host defense against viruses. Lymphocytic choriomeningitis virus (LCMV) infection induces robust type I IFN production in its natural host, the mouse. However, the mechanisms underlying the induction of type I IFNs in response to LCMV infection have not yet been clearly defined. In the present study, we demonstrate that IRF7 is required for both the early phase (day 1 postinfection) and the late phase (day 2 postinfection) of the type I IFN response to LCMV, and melanoma differentiation-associated gene 5 (MDA5)/mitochondrial antiviral signaling protein (MAVS) signaling is crucial for the late phase of the type I IFN response to LCMV. We further demonstrate that LCMV genomic RNA itself (without other LCMV components) is able to induce type I IFN responses in various cell types by activation of the RNA helicases retinoic acid-inducible gene I (RIG-I) and MDA5. We also show that expression of the LCMV nucleoprotein (NP) inhibits the type I IFN response induced by LCMV RNA and other RIG-I/MDA5 ligands. These virus-host interactions may play important roles in the pathogeneses of LCMV and other human arenavirus diseases.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhou
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cerny
authors.forename: An
authors.initials: A
authors.lastname: Zacharia
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: Kurt-Jones
authors.forename: Robert W
authors.initials: RW
authors.lastname: Finberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000072640:Interferon-Induced Helicase, IFIH1; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009698:Nucleoproteins / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D000072640:Interferon-Induced Helicase, IFIH1; D009698:Nucleoproteins; D012367:RNA, Viral; D014764:Viral Proteins; C512612:MAVS protein, mouse; C494235:Irf7 protein, mouse; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse