Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

Jennifer L. Hyde, Michael S. Diamond

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations

Abstract

N-7 and 2'-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m7GpppN; cap 1, m7GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2'-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2'-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5'-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.

Original languageEnglish
Pages (from-to)66-74
Number of pages9
JournalVirology
Volume479-480
DOIs
StatePublished - May 1 2015

Keywords

  • Immune evasion
  • Innate immunity
  • Interferon
  • Methylation
  • RNA structure
  • Viral pathogenesis

Fingerprint Dive into the research topics of 'Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation'. Together they form a unique fingerprint.

Cite this