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

Authors

  • Jenna M. Iwasenko,

    1. Virology Division, Department of Microbiology, SEALS, POWH & UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia
    2. Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia
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  • Gillian M. Scott,

    Corresponding author
    1. Virology Division, Department of Microbiology, SEALS, POWH & UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia
    2. Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia
    3. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia
    • Virology Division, Department of Microbiology, Southeastern Area Laboratory Services, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
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  • William D. Rawlinson,

    1. Virology Division, Department of Microbiology, SEALS, POWH & UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia
    2. Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia
    3. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia
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  • Anne Keogh,

    1. Heart Transplant Unit, St Vincent's Hospital, Darlinghurst, NSW, Australia
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  • Daniel Mitchell,

    1. Division of Infectious Diseases, Oregon Health and Science University and VA Medical Center, Portland, Oregon
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  • Sunwen Chou

    1. Division of Infectious Diseases, Oregon Health and Science University and VA Medical Center, Portland, Oregon
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  • The authors do not have a commercial association or other affiliation that may pose a conflict of interest.

  • All authors contributed equally to this work.

Abstract

Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most common mechanism of ganciclovir (GCV) resistance in the clinical setting. A CMV 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. J. Med. Virol. 81:507–510, 2009. © 2009 Wiley-Liss, Inc.

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