RRC ID 11800
Author Zhou S, Cerny AM, Zacharia A, Fitzgerald KA, Kurt-Jones EA, Finberg RW.
Title Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus.
Journal J. Virol.
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.
Volume 84(18)
Pages 9452-62
Published 2010-9
DOI 10.1128/JVI.00155-10
PII JVI.00155-10
PMID 20592086
PMC PMC2937596
MeSH Adaptor Proteins, Signal Transducing / metabolism Animals Cell Line DEAD Box Protein 58 DEAD-box RNA Helicases / metabolism Host-Pathogen Interactions* Humans Interferon Regulatory Factor-7 / metabolism Interferon Type I / antagonists & inhibitors* Interferon Type I / biosynthesis* Interferon-Induced Helicase, IFIH1 Lymphocytic choriomeningitis virus / immunology* Mice Mice, Knockout Nucleoproteins / immunology RNA, Viral / immunology RNA, Viral / metabolism Viral Proteins / immunology
IF 4.368
Times Cited 67
Mice IRF-7 knockout mice, C57BL/6J(RBRC01420)