Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus
Department of Medicine, Division of Infectious Diseases and Immunology
Adaptor Proteins, Signal Transducing; Animals; Cell Line; DEAD-box RNA Helicases; *Host-Pathogen Interactions; Humans; Interferon Regulatory Factor-7; Interferon Type I; Lymphocytic choriomeningitis virus; Mice; Mice, Knockout; Nucleoproteins; RNA, Viral; Viral Proteins
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.
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Citation: J Virol. 2010 Sep;84(18):9452-62. Epub 2010 Jun 30. Link to article on publisher's site
Zhou, Shenghua; Cerny, Anna M.; Zacharia, An; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; and Finberg, Robert W., "Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus" (2010). Infectious Diseases and Immunology Publications and Presentations. Paper 47.