Klin Farmakol Farm. 2004;18(2):70-74

Možnosti rychlého průkazu ganciclovir rezistentních kmenů lidského cytomegaloviru (HCMV, CMV) u pacientů po transplantaci ledviny. Detekce bodových mutací v UL97 genu HCMV spojených s rezistencí vůči gancicloviru

Jiří Psohlavec1, Miroslav Förstl1, Jiří Horáček1, Lenka Plíšková2, Zbyněk Veselský3, Petr Fixa4
1 Ústav klinické mikrobiologie FN a LF UK Hradec Králové
2 Ústav klinické biochemie a diagnostiky FN a LF UK Hradec Králové
3 Urocentrum Praha, s.r.o
4 Klinika gerontologická a metabolická, FN Hradec Králové

Keywords: ganciclovir, HCMV, resistance, UL97.

Published: December 31, 2004  Show citation

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Psohlavec J, Förstl M, Horáček J, Plíšková L, Veselský Z, Fixa P. Možnosti rychlého průkazu ganciclovir rezistentních kmenů lidského cytomegaloviru (HCMV, CMV) u pacientů po transplantaci ledviny. Detekce bodových mutací v UL97 genu HCMV spojených s rezistencí vůči gancicloviru. Klin Farmakol Farm. 2004;18(2):70-74.

Dlouhodobá léčba cytomegalovirových infekcí (CMV, HCMV) u imunokompromitovaných pacientů, zahrnujících také příjemce transplantátu ledviny, ganciclovirem může vést k selhání léčby. Rezistence vůči gancicloviru je spojená s mutacemi v UL97 regionu virového genomu a/nebo s mutacemi ve virové DNA polymeráze (UL54). UL97 gen kóduje fosfotransferázu, která je nezbytná pro monofosforylaci gancicloviru. V naší studii jsme provedli analýzu UL97 genu klinických kmenů HCMV izolovaných z pacientů po prodělané transplantaci ledviny. Tyto klinické izoláty získané z třiceti vzorků od třiceti příjemců transplantované ledviny byly amplifikovány polymerázovou řetězovou reakcí a analyzovány metodou RFLP (metoda restrikční analýzy DNA). Studovány byly specifické bodové mutace spojené s rezistencí vůči gancicloviru v kodonech 460, 520, 591, 592, 594, 595, 599, 603 a 607. Nenalezli jsme žádné izoláty obsahující kteroukoli z výše zmíněných mutací. RFLP detekce bodových mutací v HCMV UL97 genu spojených s rezistencí vůči gancicloviru může být velkým přínosem pro časnou detekci rezistence vůči gancicloviru.

POSSIBILITIES OF RAPID DETECTION OF GANCICLOVIR-RESISTANCE HUMAN CYTOMEGALOVIRUS STRAINS IN PATIENTS AFTER KIDNEY TRANSPLANTATION. DETECTION OF POINT MUTATIONS IN THE HCMV UL97 GENE ASSOCIATED WITH GANCICLOVIR RESISTANCE

Long-term treatment of HCMV-infected immunocompromised patients, including kidney transplant recipients, with ganciclovir may result in failure of threrapy. Resistance to ganciclovir is related to mutations in the UL97 region of the viral genome and/or mutations in the viral DNA polymerase (UL54). UL97 gene encoding a phosphotransferase which is essential for monophosohorylation of ganciclovir. We analyzed UL97 gene of clinical HCMV strains isolated from renal transplant recipients. These clinical isolates obtained from 30 samples of thirty renal transplant recipients were amplified by polymerase chain reaction and analyzed by RFLP analysis. The specific point mutations conferring with ganciclovir resistance, including mutations in codons 460, 520, 591, 592, 594, 595, 599, 603 and 607, were investigated. We didn´t find any isolates carried any of these mutations. RFLP detection of point mutations in HCMV UL97 gene conferring with ganciclovir resistance may be a great contribution for early detection of ganciclovir resistance.

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    References

    1. Abraham B, Lastere S, Reynes J, Bibollet-Ruche F, Vidal N. Ganciclovir resistance and UL97 gene mutations in cytomegalovirus blood isolates from patients with AIDS treated with ganciclovir. J Clin Virol. 1999; 13: 141-148. Go to original source... Go to PubMed...
    2. Baldanti F, Sarasini A, Silini E, Barbi M, Lazzarin A. Four dually resistant human cytomegalovirus strains from AIDS patients: single mutations in UL97 and UL54 open reading frames are responsible for ganciclovir- and foscarnet-specific resistance, respectively. Scand J Infect Dis Suppl. 1995; 99: 103-104.
    3. Baldanti F, Underwood MR, Talarico CL, Simoncini L, Sarasini A, Biron KK, Gerna G. The Cys607-Tyr change in the UL97 phosphotranspherase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients. Antimicrob Agents Chemother. 1998; Feb, 42 (2): 444-446. Go to original source... Go to PubMed...
    4. Baldanti F, Biron KK, Gerna G. Interpreting human cytomegalovirus antiviral drug susceptibility testing: the role of mixed virus populations. J Infect Dis. 1998; Mar. 177 (3): 823-824. Go to original source... Go to PubMed...
    5. Baldanti F, Simoncini L, Talarico CL, Sarasini A, Biron KK, Gerna G. Emergence of a ganciclovir-resistance human cytomegalovirus strain with a new UL97 mutation in an AIDS patient DNA. AIDS. 1998; May 7, 12 (7): 816-818. Go to PubMed...
    6. Baldanti F, Simoncini L, Sarasini A, Zavatoni M, Grossi P, Revallo MG, Gerna G. Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegaloviruu strains in blood. Transplantation. 1998; Aug 15, 66 (3): 324-329. Go to original source... Go to PubMed...
    7. Boivin G, Gilbert C, Morissette M, Handfield J, Goyette N. A case of ganciclovir-resistant cytomegalovirus (CMV) retinitis in a patient with AIDS: longitudinal molecular analysis of the CMV viral load and viral mutations in blood compartmets. AIDS. 1997; Jun, 11(7): 867-873. Go to original source... Go to PubMed...
    8. Chou S, Erice A, Jordan C, et al. Analysis of the UL97 phosphotranspherase coding sequence in clinical cytomegalovirus isolates and identification of mutation conferring ganciclovir resistance. J Infect Dis 1995; 171: 576-583. Go to original source... Go to PubMed...
    9. Chou S, Guentzel S, Michels KR, Miner RC, Drew WL. Frequency of UL97 phosphotranspherase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. J Infect Dis 1995; 172: 239-242. Go to original source... Go to PubMed...
    10. Chou S, Marousek G, Guentzel S, Follansbee SE, Poscher ME, Lalezari JP, Miner RC, Drew WL. Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. J Infect Dis 1997; Sep,176 (3): 786-789. Go to original source... Go to PubMed...
    11. De Clercq E. Acyclic Nucleoside Phosphonates in the Chemotherapy of DNA Virus and Retrovirus Infections. Intervirology. 1997; 40: 295-303. Go to original source... Go to PubMed...
    12. Erice A, Gil-Roda C, Pérez JL, et al. Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequenses of clinical cytomegalovirus isolates from immunocompromised patients. J Infect Dis 1997; May,175(5): 1087-1092. Go to original source... Go to PubMed...
    13. Erice A, Gil-Roda C, Pérez JL, et al. Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequenses of clinical cytomegalovirus isolates from immunocompromised patients. J Infect Dis 1997; 175: 1087-1092. Go to original source... Go to PubMed...
    14. Faizi Khan R, Mori S, Eizuru Y, Kumura Ishii K, Minamishima Y. Genetic analysis of a ganciclovir-resistant human cytomegalovirus mutant. Antiviral Res.1998; Dec, 40(1-2): 95-103. Go to original source... Go to PubMed...
    15. Hanson MN, Preheim LC, Chou S, Talarico CL, Biron KK. Novel mutation in the UL97 gene of clinical cytomegalovirus strain conferring resistance to ganciclovir. Antimicrob Agents Chemother. 1995; May, 39(5): 1204-1205. Go to original source... Go to PubMed...
    16. Liu W, Kuppermann BD, Martin DF, Wolitz RA, Margolis TP. Mutations in the cytomegalovirus UL97 gene associated with ganciclovir-resistant retinitis. J Infect Dis 1998; May, 177 (5): 1176-1181. Go to original source... Go to PubMed...
    17. Prix L, Hamprecht K, Holzhuter B, Handgretinger R, Klingebiel T. Comprehensive Restriction Analysis of the UL97 Region Allows Early Detection of Ganciclovir-Resistant Human Cytomegalovirus in an Immunocompromised Child. J Infect Dis. 1999; 180: 491-495. Go to original source... Go to PubMed...
    18. Sarasini A, Baldanti F, Furione M, Percivalle E, Brerra R, Barbi M, Gerna G. Double resistance to ganciclovir and foscarnet of four human cytomegalovirus strains recovered from AIDS patient. J Med Virol. 1995; Nov, 47 (3): 237-244. Go to original source... Go to PubMed...
    19. Smith IL, Cherrington JM, Jiles RE, Fuller MD, Freeman WR, Spector SA. High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J Infect Dis. 1997; Jul, 176 (1): 69-77. Go to original source... Go to PubMed...
    20. Snoeck R, Andrei G, De Clerc E. Patterns of resistance and sensitivity to antiviral compounds of drug-resistant strains of human cytomegalovirus selected in vitro. Eur J Clin Microbiol Infect Dis. 1996; Jul, 15 (7): 574-579. Go to original source... Go to PubMed...
    21. Wolf DG, Lee DJ, Spector SA. Detection of human cytomegalovirus mutations associated with ganciclovir resistance in cerebrospinal fluid of AIDS patient with central nervous system disease. Antimicrob Agents Chemother. 1995; Nov, 39 (11): 2552-2554. Go to original source... Go to PubMed...
    22. Zhou L, Harder TC, Ullmann U, Rautenberg P. Rapid detection by reverse hybridization of mutations in the UL97 gene of human cytomegalovirus conferring resistance to ganciclovir. J Clin Virol. 1999; 13: 53-59. Go to original source... Go to PubMed...

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