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

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VOLFOVÁ Pavlína LENGEROVÁ Martina LOCHMANOVÁ Jana DVOŘÁKOVÁ Dana ŘÍČNÁ Dita PALACKOVÁ Martina WEINBERGEROVÁ Barbora MAYER Jiří RÁČIL Zdeněk

Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Clinical Virology
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://www.sciencedirect.com/science/article/pii/S1386653214002716
Doi http://dx.doi.org/10.1016/j.jcv.2014.07.008
Obor Onkologie a hematologie
Klíčová slova HCMV resistance; Real-time PCR; Sensitive/resistant strain; Repopulation
Přiložené soubory
Popis 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.