Detection of ganciclovir resistance mutations and quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease

Guy Boivin, Sunwen Chou, Mary R. Quirk, Alejo Erice, M. Colin Jordan

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Cytomegalovirus (CMV) UL97 mutations associated with ganciclovir resistance at codons 460, 594, and 595 were detected by polymerase chain reaction (PCR) followed by restriction enzyme analysis in CMV blood isolates and directly in polymorphonuclear leukocyte (PMNL) DNA extracts of 4 subjects who died of progressive disseminated CMV disease due to ganciclovir-resistant CMV strains. The CMV DNA load was also serially determined in leukocyte fractions of these patients using a quantitative-competitive PCR assay. There was excellent concordance between specific UL97 mutations in blood culture isolates and those detected in PMNL fractions for all patients. Emergence of such UL97 mutations during ganciclovir therapy was associated with an increasing CMV DNA burden in leukocytes of the 2 patients with AIDS but not in the 2 subjects with chronic lymphocytic leukemia. Rapid molecular strategies, including detection of common CMV UL97 mutations and CMV DNA quantitation, can be used directly in leukocytes of immunocompromised subjects with CMV disease to monitor antiviral therapy.

Original languageEnglish (US)
Pages (from-to)523-528
Number of pages6
JournalJournal of Infectious Diseases
Volume173
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

Ganciclovir
Cytomegalovirus
Leukocytes
Mutation
DNA
Neutrophils
Polymerase Chain Reaction
Restriction Mapping
B-Cell Chronic Lymphocytic Leukemia
Codon
Antiviral Agents
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Detection of ganciclovir resistance mutations and quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. / Boivin, Guy; Chou, Sunwen; Quirk, Mary R.; Erice, Alejo; Colin Jordan, M.

In: Journal of Infectious Diseases, Vol. 173, No. 3, 1996, p. 523-528.

Research output: Contribution to journalArticle

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