ArticleAntimicrobial agents and chemotherapy2010
Differentiation between polymorphisms and resistance-associated mutations in human cytomegalovirus DNA polymerase.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Phenotypic evaluation of previously uncharacterized cytomegalovirus DNA polymerase sequence variants detected in a valganciclovir treatment trial.The Journal of infectious diseases · 2014Trial
- Article
- V348I mutation in UL23 gene of human herpesvirus 1 in a case of herpetic hepatitis and haemophagocytic lymphohistiocytosis.New microbes and new infections · 2019Article
- Foscarnet resistance mutations mapping to atypical domains of the cytomegalovirus DNA polymerase gene.Antiviral research · 2017Article
- The K167I variant of DNA polymerase β that is found in Esophageal Carcinoma patients impairs polymerase activity and BER.Scientific reports · 2015Article
- Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients.Computational and structural biotechnology journal · 2015Review
- Detection of cytomegalovirus drug resistance mutations by next-generation sequencing.Journal of clinical microbiology · 2013Article
- The biology of cytomegalovirus drug resistance.Current opinion in infectious diseases · 2011Review
- Recombinant phenotyping of cytomegalovirus UL54 mutations that emerged during cell passages in the presence of either ganciclovir or foscarnet.Antimicrobial agents and chemotherapy · 2011Article
- Phenotypic diversity of cytomegalovirus DNA polymerase gene variants observed after antiviral therapy.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Specific mutations in the human cytomegalovirus (HCMV) DNA polymerase (pUL54) are known to confer resistance against all currently licensed drugs for treatment of HCMV infection and disease. Following the widespread use of antivirals, the occurrence of HCMV drug resistance is constantly increasing. Recently, diagnostic laboratories have started to replace phenotypic drug resistance testing with genotypic resistance testing. However, the reliability and success of genotypic testing highly depend on the availability of high-quality phenotypic resistance data for each individual mutation and for combinations of mutations, with the latter being increasingly found in patients' HCMV isolates. We performed clonal marker transfer experiments to investigate the impacts of 7 different UL54 point mutations and also of combinations of these mutations on drug susceptibility and viral replicative fitness. We show that several mutations-S695T, A972V, K415R, S291P, and A692V-of suspected but uncertain drug susceptibility phenotype, either alone or in combination, were not relevant to antiviral drug resistance. In contrast, the combination of two mutations individually characterized previously-E756K and D413E-conferred high-grade loss of susceptibility to all three antivirals. Our results have been added to the newly available database of all published HCMV resistance mutations (http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/hcmv/index.html). These data will allow better interpretation of genotypic data and further improve the basis for drug resistance testing.
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