Manipulation of the host translation initiation complex eIF4F by DNA viruses

Derek Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

In the absence of their own translational machinery, all viruses must gain access to host cell ribosomes to synthesize viral proteins and replicate. Ribosome recruitment and scanning of capped host mRNAs is facilitated by the multisubunit eIF (eukaryotic initiation factor) 4F, which consists of a cap-binding protein, eIF4E and an RNA helicase, eIF4A, assembled on a large scaffolding protein, eIF4G. Although inactivated by many viruses to inhibit host translation, a growing number of DNA viruses are being found to employ diverse strategies to stimulate eIF4F activity in infected cells and maximize viral protein synthesis. These strategies include stimulation of cellular mTOR (mammalian target of rapamycin) signalling to inactivate 4E-BPs (eIF4E-binding proteins), a family of translational repressors that limit eIF4E availability and eIF4F complex formation, together with modulating the activity of the eIF4E kinase Mnk (mitogen-activated protein kinase signal-integrating kinase) in a variety of manners to regulate both host and viral mRNA translation. In some cases, specific viral proteins that mediate these signalling events have been identified, whereas others have been shown to interact with host translation initiation factors or complexes and modify their activity and/or subcellular localization. The present review outlines current understanding of the role of eIF4F in the life cycle of various DNA viruses and discusses its potential as a therapeutic target to suppress viral infection.

Original languageEnglish (US)
Pages (from-to)1511-1516
Number of pages6
JournalBiochemical Society transactions
Volume38
Issue number6
DOIs
StatePublished - Dec 1 2010

Keywords

  • Eukaryotic translation initiation factor 4F (eIF4F)
  • Mammalian target of rapamycin (mTOR)
  • Mitogen-activated protein kinase signal-integrating kinase (Mnk)
  • Translation initiation
  • Viral infection

ASJC Scopus subject areas

  • Biochemistry

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