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Journal of Virology, July 2005, p. 8057-8064, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8057-8064.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Regulation of the Translation Initiation Factor eIF4F by Multiple Mechanisms in Human Cytomegalovirus-Infected Cells

Derek Walsh, Cesar Perez, Joanna Notary, and Ian Mohr*

Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, New York 10016

Received 22 September 2004/ Accepted 3 February 2005

As a viral opportunistic pathogen associated with serious disease among the immunocompromised and congenital defects in newborns, human cytomegalovirus (HCMV) must engage the translational machinery within its host cell to synthesize the viral proteins required for its productive growth. However, unlike many viruses, HCMV does not suppress the translation of host polypeptides. Here, we examine how HCMV regulates the cellular cap recognition complex eIF4F, a critical component of the cellular translation initiation apparatus that recruits the 40S ribosome to the 5' end of the mRNA. This study establishes that the cap binding protein eIF4E, together with the translational repressor 4E-BP1, are both phosphorylated early in the productive viral growth cycle and that the activity of the cellular eIF4E kinase, mnk, is critical for efficient viral replication. Furthermore, HCMV replication also induces an increase in the overall abundance of eIF4F components and promotes assembly of eIF4F complexes. Notably, increasing the abundance of select eIF4F core components and associated factors alters the ratio of active eIF4F complexes in relation to the 4E-BP1 translational repressor, illustrating a new strategy through which members of the herpesvirus family enhance eIF4F activity during their replicative cycle.

* Corresponding author. Mailing address: Department of Microbiology, NYU School of Medicine, 550 First Ave., MSB 214, New York, NY 10016. Phone: (212) 263-0415. Fax: (212) 263-8276. E-mail: ian.mohr{at}med.nyu.edu.

Journal of Virology, July 2005, p. 8057-8064, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8057-8064.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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