Manipulation of the host translation initiation complex eIF4F by DNA viruses

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 elF (eukaryotic initiation factor) 4F which consists of a cap binding protein elF4E and an RNA helicase elF4A assembled on a large scaffolding protein elF4G Although inactivated by many viruses to inhibit host translation a growing number of DNA viruses are being found to employ diverse strategies to stimulate elF4F activity in infected cells and maximize viral prot in synthesis These strategies include stimulation of cellular mTOR (mammalian target of rapamycin) signalling to inactivate 4E BPs (e1F4E binding proteins) a family of translational repressors that limit elF4E availability and elF4F complex formation together with modulating the activity of the elF4E 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 elF4F in the life cycle of various DNA viruses and discusses its potential as a therapeutic target to suppress viral infection