Overview on Human Cytomegalovirus (HCMV) Resistance, and a NewTool Linking HCMV Drug Resistance Mutations to Resistance Phenotypes
Meike Chevillotte, Institute of Virology, University Hospital Ulm,
Drug resistant strains of human cytomegalovirus (HCMV) in patients at risk may increasingly develop into a problem in the clinical setting. Three systemic antiviral drugs are currently licensed to treat HCMV infection and disease: Ganciclovir, Cidofovir and Foscarnet. Although they have a different mode of action, all three antivirals share the same target, the viral DNA polymerase UL54. Ganciclovir requires initial phosphorylation to be active, which is performed by the HCMV protein kinase UL97. Specific mutations in UL97 exclusively confer reduced susceptibility to GCV. In contrast, mutations in UL54 have the potential to decrease susceptibility to any or even all three antivirals, leaving few treatment options. Genotypic resistance testing is becoming the method of choice, but requires previous phenotypic characterisation of each newly found mutation. In order to facilitate the interpretation of the patient’s HCMV sequence data, a web based search tool was generated that links the sequence to a database containing all published UL97 and UL54 mutations and corresponding antiviral drug susceptibility phenotypes (http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/hcmv/index.html). While this tool still requires clinical evaluation, it is reasonable to assume that it will provide relevant data for an adjustment of therapy and for prognosis of clinical outcome. HCMV drug susceptibility testing will become even more important once new drugs will be available for therapy allowing a wider choice of antiviral agents to treat HCMV infection.
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