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Journal of Virology, June 1999, p. 4786-4793, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Herpesvirus 8-Encoded Thymidine Kinase and Phosphotransferase Homologues Confer Sensitivity to Ganciclovir

Jennifer S. Cannon,1 Fayez Hamzeh,2 Stacy Moore,1 John Nicholas,3 and Richard F. Ambinder1,3,*

Departments of Pharmacology and Molecular Sciences,1 Medicine,2 and Oncology,3 Johns Hopkins University School of Medicine, Baltimore, Maryland

Received 15 January 1999/Accepted 17 March 1999

Human herpesvirus 8 (HHV-8) sensitivity to the nucleoside analog ganciclovir (GCV) suggests the presence of a virally encoded kinase that catalyzes the initial phosphorylation of GCV. Analysis of the HHV-8 genome identified two candidate kinases: proteins encoded by open reading frame (ORF) 21, with homology to the herpesvirus thymidine kinases (TK), and ORF 36, with homology to the herpesvirus phosphotransferases (PT). Experiments presented here show that both ORF 21 and ORF 36 encode GCV kinase activities as demonstrated by GCV phosphorylation and GCV-mediated cell death. In both regards the PT homologue ORF 36 was more active than the TK homologue ORF 21. ORF 21, but not ORF 36, weakly sensitized cells to killing by penciclovir. Neither ORF sensitized cells to killing by (E)-5-(2-bromovinyl)-2'-deoxyuridine.

* Corresponding author. Mailing address: Johns Hopkins Oncology Center, 418 N. Bond St., Baltimore, MD 21231. Phone: (410) 955-5617. Fax: (410) 955-0961. E-mail: rambind{at}jhmi.edu.

Journal of Virology, June 1999, p. 4786-4793, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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