Eukaryotic translation initiation factor 4F architectural alterations accompany translation initiation factor redistribution in poxvirus-infected cells.
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.
Walsh
Derek
D
Department of Microbiology-MSB214, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Arias
Carolina
C
Perez
Cesar
C
Halladin
David
D
Escandon
Martin
M
Ueda
Takeshi
T
Watanabe-Fukunaga
Rie
R
Fukunaga
Rikiro
R
Mohr
Ian
I
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011212:Poxviridae / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039562:Eukaryotic Initiation Factor-4F; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases