Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA

J Virol. 2013 Sep;87(18):9997-10003. doi: 10.1128/JVI.00883-13. Epub 2013 Jul 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism*
  • Encephalitis Virus, Japanese / immunology
  • Encephalitis Virus, Japanese / physiology*
  • Fibroblasts / virology
  • Host-Pathogen Interactions*
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Protein Biosynthesis
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins
  • Virus Replication*

Substances

  • Carrier Proteins
  • Ifit1 protein, mouse
  • RNA, Viral
  • RNA-Binding Proteins