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Journal of Virology, June 2006, p. 5886-5896, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02656-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cyclin-Dependent Kinase Activity Is Required for Efficient Expression and Posttranslational Modification of Human Cytomegalovirus Proteins and for Production of Extracellular Particles

Veronica Sanchez and Deborah H. Spector*

Department of Cellular and Molecular Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0712

Received 19 December 2005/ Accepted 29 March 2006

We have previously shown that the addition of the cyclin-dependent kinase (cdk) inhibitor Roscovitine at the beginning of infection of cells with human cytomegalovirus (HCMV) significantly disrupts immediate-early gene expression and the progression of the infection. In the present study, we have examined the effects of cdk inhibition on late viral events by delaying addition of Roscovitine until 24 h postinfection. Although viral DNA replication was inhibited two- to threefold by treatment of infected cells with Roscovitine, the drop did not correspond to the 1- to 2-log-unit decrease in virus titer. Quantification of viral DNA in the supernatant from cells revealed that there was a significant reduction in the production or release of extracellular particles. We observed a lag in the expression of several viral proteins but there was a significant decrease in the steady-state levels of IE2-86. Likewise, the steady-state level of the essential tegument protein UL32 (pp150) was reduced. The levels of pp150 and IE2-86 mRNA were not greatly affected by treatment with Roscovitine and thus did not correlate with the reduced levels of protein. In contrast, the expression of the tegument protein ppUL69 was higher in drug-treated samples, and the protein accumulated in a hyperphosphorylated form. ppUL69 localized to intranuclear aggregates that did not overlap with viral replication centers in cells treated with Roscovitine. Taken together, these data indicate that cdk activity is required at multiple steps during HCMV infection, including the expression, modification, and localization of virus-encoded proteins.

* Corresponding author. Mailing address: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Dr., CMM-East, Room 2059, La Jolla, CA 92093-0712. Phone: (858) 534-9737. Fax: (858) 534-6083. E-mail: dspector{at}ucsd.edu.

Journal of Virology, June 2006, p. 5886-5896, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02656-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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