Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus
Open Access
- 15 September 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (18), 9452-9462
- https://doi.org/10.1128/jvi.00155-10
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.Keywords
This publication has 71 references indexed in Scilit:
- RIG-I Detects Viral Genomic RNA during Negative-Strand RNA Virus InfectionCell, 2010
- Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligandsNature Immunology, 2009
- RIG-I-like receptors: Sensing and responding to RNA virus infectionSeminars in Immunology, 2009
- Innate instruction of adaptive immunity revisited: the inflammasomeEMBO Molecular Medicine, 2009
- TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activityNature, 2007
- The Specific and Essential Role of MAVS in Antiviral Innate Immune ResponsesImmunity, 2006
- Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virusNature, 2005
- VISA Is an Adapter Protein Required for Virus-Triggered IFN-β SignalingMolecular Cell, 2005
- Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3Cell, 2005
- Toll-like receptors and innate immunityNature Reviews Immunology, 2001