Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients

Jennifer E. Marfori, Maurice M. Exner, Gail I. Marousek, Sunwen Chou, W. Lawrence Drew

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Background: We report on two allogeneic stem cell transplant recipients who developed cytomegalovirus disease associated with new viral mutations that conferred antiviral drug resistance. Methods: Blood specimens obtained during symptomatic disease were analyzed for mutations in the CMV UL97 and DNA polymerase genes and new mutations were assessed by recombinant phenotyping. Results: Rising cytomegalovirus (CMV) antigenemia occurred after 4-5 months of preemptive valganciclovir therapy, followed by symptomatic CMV disease including fatal pneumonia in one case. In one case, a new viral UL97 mutation (deletion of codons 601-603) was found which conferred 15-fold increased ganciclovir resistance. In the other case, a known UL97 resistance mutation M460V and a new DNA polymerase (pol) mutation D413A were found. D413A conferred ganciclovir and cidofovir resistance. Conclusions: Known and newly discovered drug resistance mutations arising during preemptive therapy may complicate post-transplant CMV disease in stem cell recipients. Improved recombinant phenotyping methods enable the rapid quantitation of the resistance conferred by newly identified UL97 and pol mutations.

Original languageEnglish (US)
Pages (from-to)120-125
Number of pages6
JournalJournal of Clinical Virology
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Cytomegalovirus
  • Resistance
  • Stem cell transplant

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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