Publication:
Investigation of ganciclovir resistance in cytomegalovirus isolates by phenotypic and genotypic methods

dc.contributor.authorSarınoğlu, Rabia Can
dc.contributor.authorÇolak, Dilek
dc.contributor.authorKüpesiz, Osman Alphan
dc.contributor.authorKuşkuçu, Mert Ahmet
dc.contributor.authorYalçın, Koray
dc.contributor.authorSaglık, İmran
dc.contributor.authorMutlu, Derya
dc.contributor.authorMidilli, Kenan
dc.contributor.authorPeker, Bilal Olcay
dc.contributor.authorÖzhak, Betil
dc.contributor.authorÖzkul, Aykut
dc.contributor.authorFoldes, Kataline
dc.contributor.buuauthorSAĞLIK, İMRAN
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı
dc.contributor.orcid0000-0003-0864-4989
dc.contributor.researcheridA-4970-2019
dc.date.accessioned2024-11-08T12:12:08Z
dc.date.available2024-11-08T12:12:08Z
dc.date.issued2023-07-01
dc.description.abstractGanciclovir-resistant cytomegalovirus (CMV) strains are reported following long-term antiviral agent use, especially for immune-suppressive patients. In this study, it was aimed to investigate the mutations in the UL97 gene of CMV, which causes ganciclovir (GCV) resistance by genotypic and phenotypic methods in patients who developed CMV infection following hematopoietic cell (HCT) or solid organ transplantation (SOT). Thirty patients who had HCT or SOT in Mediterranean University Hospital and developed CMV infection during routine follow-up with a viral load of CMV over 1000 copies/mL were included in the study. CMV DNA was analyzed by an automated system (Cobas Ampliprep/COBAS TaqMan CMV Test, Roche Diagnostics, Germany) quantitatively. DNA sequence analysis of the regions including codons 420-664 in the UL97 gene region was done by the Sanger sequencing method to detect mutations causing antiviral resistance and compared with defined mutations. In order to investigate antiviral resistance by phenotypic methods, heparinized blood samples of the patients were collected, 'buffy coat (leukocyte layer)' was inoculated into MRC-5 cells by centrifugation method and CMV growth in these cells was controlled with monoclonal antibodies when growth was detected, virus titer was determined and plaque reduction test was applied as recommended. It was determined that 22 of the 30 patients were HCT recipients and eight were SOT (five kidney, three liver) recipients. When the CMV serology pattern of the patients was evaluated before transplantation, 29 (96.7%) patients were found to be seropositive and one (3.3%) patient was found to be seronegative. Totally, nine CMV UL97 mutations were detected in seven (23.3%) pediatric patients who had HCT, including six seropositive and one seronegative case. In addition, one mutation (D605E) not known to cause GCV resistance was detected in a seronegative recipient and three previously unidentified mutations were detected (1474T, F499S, V559A) in a seronegative recipient. Five of the mutations defined were UL97 mutations with a defined clinical resistance against GCV in each of the five recipients (C603W, C592G, H520Q, M460V, A594T). In the plaque reduction test using 3 mu M, 12 mu M, 48 mu M and 96 mu M concentrations of GCV in CMV strains, the IC50 value was determined to be >= 8 mu M for the five CMV strains, and the phenotypic presence of GCV resistance was shown. Clinical resistance associated with CMV UL97 mutation was detected in five (22.7%) of 22 patients who had HCT. GCV resistance was also demonstrated in these patients by phenotypic methods. No UL97 mutation was detected in the patients who had SOT.
dc.identifier.doi10.5578/mb.20239933
dc.identifier.endpage418
dc.identifier.issn0374-9096
dc.identifier.issue3
dc.identifier.startpage401
dc.identifier.urihttps://doi.org/10.5578/mb.20239933
dc.identifier.urihttps://www.mikrobiyolbul.org/managete/fu_folder/2023-03/401-418%20Dilek%20Colak.pdf
dc.identifier.urihttps://hdl.handle.net/11452/47644
dc.identifier.volume57
dc.identifier.wos001070931100006
dc.indexed.wosWOS.SCI
dc.language.isoen
dc.publisherAnkara Mikrobiyoloji
dc.relation.journalMikrobiyoloji Bülteni
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDrug-resistance
dc.subjectUl97 gene
dc.subjectMutations
dc.subjectTransplantation
dc.subjectInfection
dc.subjectValganciclovir
dc.subjectEmergence
dc.subjectTherapy
dc.subjectCmv
dc.subjectPhenotypic method
dc.subjectGcv resistance
dc.subjectUl97
dc.subjectTransplantation
dc.subjectScience & technology
dc.subjectLife sciences & biomedicine
dc.subjectMicrobiology
dc.titleInvestigation of ganciclovir resistance in cytomegalovirus isolates by phenotypic and genotypic methods
dc.typeArticle
dspace.entity.typePublication
relation.isAuthorOfPublicationaab7d5dd-72a4-4f3a-a677-1fdf3e13cadc
relation.isAuthorOfPublication.latestForDiscoveryaab7d5dd-72a4-4f3a-a677-1fdf3e13cadc

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Sağlık_vd_2023.pdf
Size:
597.05 KB
Format:
Adobe Portable Document Format

Collections