Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir

Sunwen Chou, Rachel H. Waldemer, Anne E. Senters, Kevin S. Michels, George W. Kemble, Richard C. Miner, W. Lawrence Drew

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Most ganciclovir (GCV)-resistant cytomegalovirus (CMV) isolates contain UL97 gene mutations at codon 460 or 520 or between codons 590 and 607, where an increasing variety of mutations have been detected, including deletions. To determine their phenotypic effect, 9 UL97 mutations not previously studied were transferred to drug-sensitive laboratory CMV strains that contained unique restriction sites developed for this purpose. Deletion of the entire codon range 591-607 conferred a 6-fold increase in GCV resistance, with little effect on viral replication. Some mutations found in clinical isolates, including C592G and A594T, conferred only 2-3-fold decreases in GCV susceptibility. For C592G, this phenotype was confirmed by transfer to different CMV strains and by restoration of full drug susceptibility after removal of the mutation. Low drug levels resulting from oral GCV therapy may predispose the virus to the initial selection of these low-grade UL97 resistance mutations and to later accumulation of other mutations and greater resistance.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalJournal of Infectious Diseases
Volume185
Issue number2
DOIs
StatePublished - Jan 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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