Detecting human cytomegalovirus drug resistant mutations and monitoring the emergence of resistant strains using real-time PCR
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25130511
DOI
10.1016/j.jcv.2014.07.008
PII: S1386-6532(14)00271-6
Knihovny.cz E-resources
- Keywords
- HCMV resistance, Real-time PCR, Repopulation, Sensitive/resistant strain,
- MeSH
- Antiviral Agents therapeutic use MeSH
- Cytomegalovirus Infections drug therapy virology MeSH
- Cytomegalovirus drug effects genetics isolation & purification MeSH
- Molecular Diagnostic Techniques methods MeSH
- Adult MeSH
- Transplantation, Homologous adverse effects MeSH
- Real-Time Polymerase Chain Reaction methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation, Missense * MeSH
- Treatment Failure MeSH
- Polymorphism, Restriction Fragment Length MeSH
- Sequence Analysis, DNA MeSH
- Hematopoietic Stem Cell Transplantation adverse effects MeSH
- Drug Resistance, Viral * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiviral Agents MeSH
BACKGROUND: Antiviral resistance development is a serious complication of human cytomegalovirus virostatic therapy caused by mutations in UL 97 and/or UL54 genes. OBJECTIVES: To determinate the presence of sensitive and resistant strains in patients developing antiviral resistance. STUDY DESIGN: We used three different molecular biological methods for mutation analysis-restriction fragment length polymorphism, sequencing and real-time PCR approach. RESULTS: We describe three allogeneic hematopoietic stem cell transplant patients developing the GCV resistant HCMV strains manifested by virostatic treatment failure. In these patients we identified UL97 mutations L595S, A594V and A594T and monitored the dynamics of coexisted sensitive/resistant strains. We confirmed the presence of mixed HCMV populations and in two patients a phenomenon of sensitive strain repopulation which occurred after 6.5 months and 1 month after removing GCV pressure. CONCLUSIONS: Our results show changes in proportions of sensitive/resistant subpopulations over time but other studies would be required to demonstrate the beneficial impact of their monitoring on clinical outcome.
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
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