Source:http://linkedlifedata.com/resource/pubmed/id/12181449
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2002-8-15
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
62
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
714-21
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12181449-Amino Acid Sequence,
pubmed-meshheading:12181449-Antiviral Agents,
pubmed-meshheading:12181449-Ganciclovir,
pubmed-meshheading:12181449-Genes, Viral,
pubmed-meshheading:12181449-Herpesvirus 6, Human,
pubmed-meshheading:12181449-Humans,
pubmed-meshheading:12181449-Microbial Sensitivity Tests,
pubmed-meshheading:12181449-Molecular Sequence Data,
pubmed-meshheading:12181449-Phosphorylation,
pubmed-meshheading:12181449-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:12181449-Recombinant Proteins,
pubmed-meshheading:12181449-Sequence Homology, Amino Acid,
pubmed-meshheading:12181449-T-Lymphocytes,
pubmed-meshheading:12181449-Tumor Cells, Cultured,
pubmed-meshheading:12181449-Vaccinia virus
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pubmed:year |
2002
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pubmed:articleTitle |
Role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of ganciclovir.
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pubmed:affiliation |
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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