Journal
JOURNAL OF VIROLOGY
Volume 87, Issue 18, Pages 9997-10003Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00883-13
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Funding
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Osaka Foundation for Promotion of Clinical Immunology
- Grants-in-Aid for Scientific Research [24390120, 25115511] Funding Source: KAKEN
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The interferon-inducible protein with tetratricopeptide (IFIT) family proteins inhibit replication of some viruses by recognizing several types of RNAs, including 5'-triphosphate RNA and 5' capped 2'-O unmethylated mRNA. However, it remains unclear how IFITs inhibit replication of some viruses through recognition of RNA. Here, we analyzed the mechanisms by which Ifit1 exerts antiviral responses. Replication of a Japanese encephalitis virus (JEV) 2'-O methyltransferase (MTase) mutant was markedly enhanced in mouse embryonic fibroblasts and macrophages lacking Ifit1. Ifit1 bound 5'-triphosphate RNA but more preferentially associated with 5' capped 2'-O unmethylated mRNA. Ifit1 inhibited the translation of mRNA and thereby restricted the replication of JEV mutated in 2'-O MTase. Thus, Ifit1 inhibits replication of MTase-defective JEV by inhibiting mRNA translation through direct binding to mRNA 5' structures.
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