Mutation in region III of the DNA polymerase gene conferring foscarnet resistance in cytomegalovirus isolates from 3 subjects receiving prolonged antiviral therapy

Sunwen Chou, Gail Marousek, David M. Parenti, Shelley M. Gordon, Alison G. Lavoy, Jennifer G. Ross, Richard C. Miner, W. Lawrence Drew

Research output: Contribution to journalArticle

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Abstract

Three human immunodeficiency virus-infected subjects with progressive cytomegalovirus (CMV) retinitis despite prolonged antiviral therapy had buffy coat CMV isolates that were resistant to both ganciclovir and foscarnet. Genetic analysis of the resistant isolates showed that each contained a well- known ganciclovir resistance mutation in the viral UL97 phosphotransferase sequence, as well as a mutation (Ala to Val at codon 809, V809) in conserved region III of the DNA polymerase (Pol) sequence. A segment of the Pol sequence from one of the clinical isolates was transferred to CMV laboratory strain AD169 by homologous recombination. The recombinant virus containing V809 showed 6.3-fold increased foscarnet resistance and 2.6-fold increased ganciclovir resistance. Occurrence of the V809 mutation in 3 unrelated cases suggests that it is a clinically significant viral genetic marker for foscarnet resistance and decreased susceptibility to ganciclovir.

Original languageEnglish (US)
Pages (from-to)526-530
Number of pages5
JournalJournal of Infectious Diseases
Volume178
Issue number2
StatePublished - 1998
Externally publishedYes

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DNA Polymerase III
Foscarnet
Ganciclovir
Cytomegalovirus
Antiviral Agents
Mutation
Genes
Cytomegalovirus Retinitis
Homologous Recombination
Therapeutics
Genetic Markers
Codon
Phosphotransferases
Biomarkers
HIV
Viruses

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Mutation in region III of the DNA polymerase gene conferring foscarnet resistance in cytomegalovirus isolates from 3 subjects receiving prolonged antiviral therapy. / Chou, Sunwen; Marousek, Gail; Parenti, David M.; Gordon, Shelley M.; Lavoy, Alison G.; Ross, Jennifer G.; Miner, Richard C.; Drew, W. Lawrence.

In: Journal of Infectious Diseases, Vol. 178, No. 2, 1998, p. 526-530.

Research output: Contribution to journalArticle

Chou, Sunwen ; Marousek, Gail ; Parenti, David M. ; Gordon, Shelley M. ; Lavoy, Alison G. ; Ross, Jennifer G. ; Miner, Richard C. ; Drew, W. Lawrence. / Mutation in region III of the DNA polymerase gene conferring foscarnet resistance in cytomegalovirus isolates from 3 subjects receiving prolonged antiviral therapy. In: Journal of Infectious Diseases. 1998 ; Vol. 178, No. 2. pp. 526-530.
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