Human herpesvirus 8-encoded thymidine kinase and phoshpotransferase homologues confer sensitivity to ganciclovir

Jennifer S. Cannon, Fayez Hamzeh, Stacy Moore, John Nicholas, Richard F. Ambinder

Research output: Contribution to journalArticlepeer-review

Abstract

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-4 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 homolog to the herpesvirus phoshotransferase (PT). Experimental 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-(bromovinyl)-2'- deoxyuridine.

Original languageEnglish (US)
Pages (from-to)4786-4793
Number of pages8
JournalJournal of virology
Volume73
Issue number6
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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