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Detecting human cytomegalovirus drug resistant mutations and monitoring the emergence of resistant strains using real-time PCR.

作者信息

Volfova Pavlina, Lengerova Martina, Lochmanova Jana, Dvorakova Dana, Ricna Dita, Palackova Martina, Weinbergerova Barbora, Mayer Jiri, Racil Zdenek

机构信息

Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.

Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

出版信息

J Clin Virol. 2014 Oct;61(2):270-4. doi: 10.1016/j.jcv.2014.07.008. Epub 2014 Jul 22.

DOI:10.1016/j.jcv.2014.07.008
PMID:25130511
Abstract

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.

摘要

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