Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus
Authors
Zhou, ShenghuaCerny, Anna M.
Zacharia, An
Fitzgerald, Katherine A
Kurt-Jones, Evelyn A.
Finberg, Robert W.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2010-07-02Keywords
Adaptor Proteins, Signal TransducingAnimals
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
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
J Virol. 2010 Sep;84(18):9452-62. Epub 2010 Jun 30. Link to article on publisher's siteDOI
10.1128/JVI.00155-10Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35210PubMed ID
20592086Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/JVI.00155-10