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Journal of Virology, November 2007, p. 11730-11736, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.02760-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nuclear Export of the Human Cytomegalovirus Tegument Protein pp65 Requires Cyclin-Dependent Kinase Activity and the Crm1 Exporter{triangledown}

Veronica Sanchez,1 Jeffrey A. Mahr,2 Nicole I. Orazio,3 and Deborah H. Spector2*

Department of Microbial and Molecular Pathogenesis, Texas A & M Health Science Center, College Station, Texas 77843,1 Department of Cellular and Molecular Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences,2 Division of Biological Sciences, University of California, San Diego, La Jolla, California 920933

Received 14 December 2006/ Accepted 9 August 2007

We have previously shown that treatment of human cytomegalovirus-infected cells with the cyclin-dependent kinase (cdk) inhibitor roscovitine has significant effects on several stages of the virus life cycle depending on the time of addition (V. Sanchez, A. K. McElroy, J. Yen, S. Tamrakar, C. L. Clark, R. A. Schwartz, and D. H. Spector, J. Virol. 78:11219-11232, 2004; V. Sanchez and D. Spector, J. Virol. 80:5886-5896, 2006). In this report, we add to these findings by demonstrating alterations in the phosphorylation and localization of pp65 (UL83) in cells treated with roscovitine. We observed that inhibition of cdk activity causes the retention of pp65 within the nucleus at late times postinfection. At the same time, we observed a change in the phosphorylation pattern of the protein. Interestingly, mutation of potential cdk phosphorylation sites did not affect the ability of pp65 to localize to the nucleus or to relocalize to the cytoplasm late in infection. However, we found that the cytoplasmic accumulation of pp65 late in infection was sensitive to the Crm1 inhibitor leptomycin B.


* Corresponding author. Mailing address: 9500 Gilman Dr., PSB 3254, La Jolla, CA 92093-0712. Phone: (858) 822-4003. Fax: (858) 534-6083. E-mail: dspector{at}ucsd.edu

{triangledown} Published ahead of print on 22 August 2007.


Journal of Virology, November 2007, p. 11730-11736, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.02760-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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