Monitoring of resistanceassociated mutations in UL97 gene of cytomegalovirus in children after allogeneic hematopoietic stem cell transplantation

Abstract

Objective. To perform genotyping of cytomegalovirus (CMV) phosphotransferase UL97 and investigate mutations associated with ganciclovir/valganciclovir (GCV/VGCV) resistance in children after allogeneic hematopoietic stem cell transplantation (HSCT) with confirmed CMV infection. Materials and Methods. This single-center prospective study was conducted from January 2020 to December 2021 and enrolled allogeneic HSCT recipients under 18 years of age with confirmed CMV infection. In case of possible GCV resistance, molecular genotyping with Sanger sequencing was performed. The search for mutations in the UL97 gene was carried out in the range of 425–670 codons. Results. Out of 168 patients with confirmed CMV infection, 72 patients met the criteria for possible resistance to GCV/VGCV. As a result of nucleotide sequencing of the CMV UL97 gene in 19 patients (11.3% of a total number of patients and 26.4% of patients meeting the resistance criteria) 11 genotypes of the following mutations were identified: H520Q, C592G, A594V, L595S, D605E, C603W, C607Y, C607F, M615V, M460V and E655K. The following mutations associated with resistance to HCV/VHCV: H520Q, C592G, A594V, L595S, C603W, C607Y, C607F, M460V were found in 12 patients (7% of a total number of patients and 9.7% of patients meeting the resistance criteria). Conclusions. Due to a high frequency of detection of the mutant form of phosphotransferase UL97 in allogeneic HSCT recipients with confirmed CMV infection, it is important to implement monitoring of resistant-associated mutations in order to administer appropriate antiviral therapy.