PT  - JOURNAL ARTICLE
AU  - Leen De Bolle
AU  - Detlef Michel
AU  - Thomas Mertens
AU  - Chaysavanh Manichanh
AU  - Henri Agut
AU  - Erik De Clercq
AU  - Lieve Naesens
TI  - Role of the Human Herpesvirus 6 U69-Encoded Kinase in the Phosphorylation of Ganciclovir
AID  - 10.1124/mol.62.3.714
DP  - 2002 Sep 01
TA  - Molecular Pharmacology
PG  - 714--721
VI  - 62
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/62/3/714.short
4100  - http://molpharm.aspetjournals.org/content/62/3/714.full
SO  - Mol Pharmacol2002 Sep 01; 62
AB  - The human herpesvirus 6 (HHV-6) U69 gene product (pU69) is the presumed functional homolog of the human cytomegalovirus (HCMV) UL97-encoded kinase (pUL97), which converts ganciclovir to its monophosphate metabolite in HCMV-infected cells. It has been reported that insertion of U69 into baculovirus confers sensitivity to ganciclovir in insect cells (J Virol 73:3284–3291, 1999). Our metabolic studies in HHV-6–infected human T-lymphoblast cells indicated that the efficiency of ganciclovir phosphorylation induced by HHV-6 was relatively poor. Recombinant vaccinia viruses (rVVs), expressing high levels of pU69 from two HHV-6 strains (representing the A and B variant), were constructed and used to compare the ganciclovir-phosphorylating capacity of pU69 and pUL97 in human cells. Metabolic studies with [8-3H]ganciclovir showed that ganciclovir was phosphorylated in human cells infected with pU69-expressing rVVs, although the levels of phosphorylated ganciclovir metabolites were approximately 10-fold lower than those observed with pUL97. We also demonstrated that pU69, like pUL97, is expressed as a nuclear protein. Our results indicate that the limited phosphorylation of ganciclovir by pU69 may contribute to its modest antiviral activity against HHV-6 in certain cell systems.