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Title: Ganciclovir-resistant post-transplant cytomegalovirus infection due to combined deletion mutation at codons 595-596 of the UL97 gene.
Authors: Leung, Po Yee Mia;Tran, Thomas;Testro, Adam;Paizis, Kathy;Kwong, Jason C;Whitlam, John B
Affiliation: Virus Identification Laboratory, Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia
Department of Medicine, University of Melbourne, Melbourne, Vic., Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia
Department of Nephrology, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Dec-2019
EDate: 2019-12
Citation: Transplant infectious disease : an official journal of the Transplantation Society 2019; 21(6): e13168
Abstract: The development of antiviral-resistant cytomegalovirus (CMV) infection complicates the management of transplant recipients. We describe the case of a 65-year-old male who developed CMV disease on valganciclovir prophylaxis (donor CMV IgG positive, recipient CMV IgG indeterminate) 30┬ádays after combined liver-kidney transplantation for alcoholic cirrhosis and hepato-renal syndrome. After an initial complete response to treatment dose oral valganciclovir, he developed recurrent CMV viraemia. Resistance testing revealed a UL97 mutation with in-frame deletions of codons 595-596. He was treated successfully with foscarnet and reduction in immunosuppression. This mutation has not been described previously and was suspected to confer ganciclovir resistance. Ganciclovir resistance occurs most commonly due to mutations in the UL97 or UL54 genes, which encode a protein kinase and a DNA polymerase, respectively. The UL97-encoded protein kinase phosphorylates ganciclovir to ganciclovir triphosphate, which competitively inhibits viral replication. Mutations in the UL97 gene are typically point mutations or deletions. We describe a new mutation, del595-596 in the CMV UL97 gene, occurring in the context of clinical treatment failure with standard and double-dose ganciclovir, and successful virological control achieved with foscarnet. This mutation is likely to result in ganciclovir resistance, although recombinant phenotyping is required for confirmation.
DOI: 10.1111/tid.13168
ORCID: 0000-0002-3736-0777
PubMed URL: 31498954
Type: Case Reports
Journal Article
Subjects: UL97 gene
cytomegalovirus infection
ganciclovir resistance
kidney transplant
liver transplant
Appears in Collections:Journal articles

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