Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D

Jenna M. Iwasenko, Gillian M. Scott, William D. Rawlinson, Anne Keogh, Daniel Mitchell, Sunwen Chou

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most common mechanism of ganciclovir (GCV) resistance in the clinical setting. ACMV strain with a previously unrecognized UL97 mutation N597D was identified in the blood of a heart transplant recipient who experienced a persistent CMV infection with high viral loads accompanying pain and fever while receiving valganciclovir (valGCV) therapy. The N597D mutation was transferred by mutagenesis to an antiviral sensitive CMV strain for analysis of antiviral susceptibility by standardized phenotypic assay. Recombinant phenotyping showed N597D conferred a less than twofold increase in GCV IC50 compared to the sensitive control strain. Despite the presence of this mutation, valGCV eventually resolved the infection after 6 weeks of therapy. A subsequent CMV reactivation was also responsive to valganciclovir. This case illustrates the diversity of UL97 mutations in the codon segment 590-607 usually associated with GCV resistance, with some mutations producing minimal levels of resistance that do not preclude a therapeutic response to the drug. Accurate interpretation of genotypic test results ultimately requires experimental determination of the level of resistance conferred by newly discovered UL97 mutations.

Original languageEnglish (US)
Pages (from-to)507-510
Number of pages4
JournalJournal of Medical Virology
Volume81
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Cytomegalovirus Infections
Transplants
Mutation
Ganciclovir
Cytomegalovirus
Therapeutics
Antiviral Agents
valganciclovir
Viral Load
Codon
Mutagenesis
Protein Kinases
Inhibitory Concentration 50
Fever
Pain
Infection
Pharmaceutical Preparations

Keywords

  • Antiviral resistance
  • Heart transplant
  • Human cytomegalovirus
  • Protein kinase

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D. / Iwasenko, Jenna M.; Scott, Gillian M.; Rawlinson, William D.; Keogh, Anne; Mitchell, Daniel; Chou, Sunwen.

In: Journal of Medical Virology, Vol. 81, No. 3, 03.2009, p. 507-510.

Research output: Contribution to journalArticle

Iwasenko, Jenna M. ; Scott, Gillian M. ; Rawlinson, William D. ; Keogh, Anne ; Mitchell, Daniel ; Chou, Sunwen. / Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D. In: Journal of Medical Virology. 2009 ; Vol. 81, No. 3. pp. 507-510.
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