PMID- 12181449
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 62
IP  - 3
DP  - 2002 Sep
TI  - Role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of 
      ganciclovir.
PG  - 714-21
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-(3)H]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.
FAU - De Bolle, Leen
AU  - De Bolle L
AD  - Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, 
      Belgium.
FAU - Michel, Detlef
AU  - Michel D
FAU - Mertens, Thomas
AU  - Mertens T
FAU - Manichanh, Chaysavanh
AU  - Manichanh C
FAU - Agut, Henri
AU  - Agut H
FAU - De Clercq, Erik
AU  - De Clercq E
FAU - Naesens, Lieve
AU  - Naesens L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antiviral Agents)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (pU69 kinase, human herpesvirus 6)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antiviral Agents/*metabolism/pharmacology
MH  - Ganciclovir/*metabolism/pharmacology
MH  - Genes, Viral/physiology
MH  - Herpesvirus 6, Human/drug effects/*enzymology/genetics
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Sequence Homology, Amino Acid
MH  - T-Lymphocytes/virology
MH  - Tumor Cells, Cultured/virology
MH  - Vaccinia virus/drug effects/genetics
EDAT- 2002/08/16 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/08/16 10:00
PHST- 2002/08/16 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/08/16 10:00 [entrez]
AID - 10.1124/mol.62.3.714 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2002 Sep;62(3):714-21. doi: 10.1124/mol.62.3.714.