Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus.
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.
Zhou
Shenghua
S
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Cerny
Anna M
AM
Zacharia
An
A
Fitzgerald
Katherine A
KA
Kurt-Jones
Evelyn A
EA
Finberg
Robert W
RW
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
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