Genetic analysis of a ganciclovir-resistant human cytomegalovirus mutant

Rounak Faizi Khan, Seiichiro Mori, Yoshito Eizuru, Keiko Kumura Ishii, Yoichi Minamishima

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18 Citations (Scopus)

Abstract

We isolated a ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) from a laboratory strain, AD169, and analysed the mutant. Attempts were also made to identify directly the mutated gene. The 50% inhibitory concentration (IC50) of GCV for the mutant strain was five times higher than that of the wild-type strain. The mutant strain showed similar sensitivity to phosphonoacetic acid and cidofovir as the wild-type strain. These data suggest mutation in the UL97 gene encoding for the phosphotransferase that phosphorylates GCV. Molecular analysis of the mutant strain revealed that a single base substitution of adenine by cytosine occurred at the 1796 nucleotide position of the UL97 gene region, resulting in the substitution of lysine by threonine at codon 599 in the UL97 gene product. Marker transfer experiment confirmed that this mutation conferred HCMV resistance to GCV. The mutation at codon 599 was easily identified by means of RsaI digestion of the selected PCR product. Copyright (C) 1998 Published by Elsevier Science B.V.

Original languageEnglish
Pages (from-to)95-103
Number of pages9
JournalAntiviral Research
Volume40
Issue number1-2
DOIs
Publication statusPublished - 1998 Dec

Keywords

  • Cidofovir
  • Ganciclovir
  • Phosphonoacetic acid
  • UL97 mutation

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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