The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication

Gierman, Todd; Frederickson, Robert; Sonenberg, Nahum; Pickup, David J.

doi:10.1016/0042-6822(92)90557-6

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…There are reports which show that vaccinia virus selectively translates its own mRNAs, and it is not known whether T7-generated RNAs would be seen as virus or host derived in this context (1,4). These observations are balanced by reports which show that vaccinia virus does not modify eukaryotic initiation factors and acts rather to normalize translation by preventing the activities of double-stranded-RNAdependent and heme-dependent eukaryotic initiation factor 2 kinases (5,7,11,17,37,43,58). In this study, levels of E7 translation were measured relative to those with control monocistronic constructs in identical vector backgrounds and so would be insensitive to variations in overall translation efficiency.…”

Section: Discussionmentioning

confidence: 99%

Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame

Stacey

Jordan

Snijders

et al. 1995

J Virol

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In this study we investigated the translational capacities of bicistronic and spliced mRNAs originating from the E6 and E7 regions of the high-risk genital human papillomavirus type 16 (HPV-16) and the low-risk HPV-11. For HPV-16 it was found, unexpectedly, that E7 protein could be translated from full-length bicistronic E6-E7 mRNAs. E6*I and E6*II splicing events were not required for E7 synthesis, nor did splicing increase the efficiency of E7 translation significantly. In cells, E7 synthesis from all known naturally occurring mRNA structures was very inefficient compared with that from synthetic monocistronic controls, suggesting that HPV-16 employs translational mechanisms to restrict E7 protein levels. For HPV-11, only RNAs initiated at the P 264 promoter, located within the E6 open reading frame, were capable of providing an efficient template for E7 synthesis. P 264-initiated mRNAs were as efficient in vivo as monocistronic controls, suggesting that the low-risk HPV-11 does not limit E7 synthesis by translational mechanisms. A detailed analysis of HPV-16 templates by using site-directed mutagenesis showed that the majority of ribosomes which ultimately translate E7 have not reinitiated after translating some or all of the upstream open reading frames. The data support a model in which the failure of 40S ribosomal initiation complexes to recognize the E6 AUG renders them capable of proceeding efficiently to translate E7.

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Section: Discussionmentioning

confidence: 99%

Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame

Stacey

Jordan

Snijders

et al. 1995

J Virol

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“…Early studies focused largely on the fact that VACV did not negatively affect eIF4F function, in contrast with many other viruses being studied at that time [44,45]. Indeed, poxvirus mRNAs were found to be translated in a cap-dependent manner albeit with a reduced dependence upon initiation factors compared with host mRNAs [46][47][48][49].…”

Section: Poxvirusesmentioning

confidence: 99%

Manipulation of the host translation initiation complex eIF4F by DNA viruses

Walsh

2010

Biochemical Society Transactions

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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.

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“…Earlier studies claimed that translation in poxvirusinfected cells proceeded normally in cells engineered to induc-ibly express the poliovirus 2A protease (29), while a different study reported that eIF4G cleavage by poliovirus 2A inhibits translation in poxvirus-infected cells (5). In a similar vein, studies of eIF4E modification in poxvirus-infected cells focused exclusively on the lack of apparent dephosphorylation (15,38). Finally, none of these studies was performed with normal cells; instead, they relied exclusively on transformed, immortalized cell lines now known to contain altered translational regulatory pathways (37).…”

mentioning

confidence: 98%

Eukaryotic Translation Initiation Factor 4F Architectural Alterations Accompany Translation Initiation Factor Redistribution in Poxvirus-Infected Cells

Walsh

Arias

Perez

et al. 2008

Molecular and Cellular Biology

143

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Despite their self-sufficient ability to generate capped mRNAs from cytosolic DNA genomes, poxviruses must commandeer the critical eukaryotic translation initiation factor 4F (eIF4F) to recruit ribosomes. While eIF4F integrates signals to control translation, precisely how poxviruses manipulate the multisubunit eIF4F, composed of the cap-binding eIF4E and the RNA helicase eIF4A assembled onto an eIF4G platform, remains obscure. Here, we establish that the poxvirus infection of normal, primary human cells destroys the translational repressor eIF4E binding protein (4E-BP) and promotes eIF4E assembly into an active eIF4F complex bound to the cellular polyadenylate-binding protein (PABP). Stimulation of the eIF4G-associated kinase Mnk1 promotes eIF4E phosphorylation and enhances viral replication and protein synthesis. Remarkably, these eIF4F architectural alterations are accompanied by the concentration of eIF4E and eIF4G within cytosolic viral replication compartments surrounded by PABP. This demonstrates that poxvirus infection redistributes, assembles, and modifies core and associated components of eIF4F and concentrates them within discrete subcellular compartments. Furthermore, it suggests that the subcellular distribution of eIF4F components may potentiate the complex assembly.

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The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication

Cited by 14 publications

References 38 publications

Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame

Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame

Manipulation of the host translation initiation complex eIF4F by DNA viruses

Eukaryotic Translation Initiation Factor 4F Architectural Alterations Accompany Translation Initiation Factor Redistribution in Poxvirus-Infected Cells

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