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 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.
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. derek.walsh@dcu.ie
Derek
D
Walsh
D004267:DNA Viruses / Q000235:genetics* / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012315:RNA Caps / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis; D014777:Virus Diseases / Q000628:therapy
D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D012315:RNA Caps; D014764:Viral Proteins; D039601:Eukaryotic Initiation Factor-4A