Study of the ganciclovir resistant UL54 gene mutations in cytomegalovirus infected Kidney and Hematopoietic stem cell transplant recipients
Subject Areas : Virology
1 - 2- استادیار، مرکز تحقیقات پیوند اعضا، دانشکده علوم پزشکی شیراز،شیراز، ایران
Keywords: Kidney transplantation, Hematopoietic stem cell transplantation, Cytomegalovirus, Drug resistance,
Abstract :
Background & Objectives: Cytomegalovirus resistance to ganciclovir with specific mutations in the UL97 and UL54 genes is a factor in treatment failure and disease progression in organ transplant recipients, especially Kidney and Hematopoietic Stem Cell Transplant recipients. This study aimed to determine the mutations leading to resistance in the UL54 and UL97 genes of human cytomegalovirus. Materials and Methods: In this study after examining samples from 25 Kidney and Hematopoietic Stem Cell Transplant recipients between 2015 and 2017 with viral load ≥ 10,000 copies/mL, six samples were selected for sequencing of the UL54 gene using the Sanger method using the Nested-PCR method. Finch software (version 1.4.0) was used to analyze the sequencing results. Results: After sequencing, no known mutations were observed in 4 Kidney transplant recipients. On the other hand, a serine 882 insertion mutation in the UL54 gene was observed in 1 Hematopoietic Stem Cell Transplant recipient. Also, the phylogenetic tree of the UL54 gene showed that the Iranian isolate ancestrally belongs to 20 reference strains, including the Merlin strain. Conclusion: Considering that ganciclovir treatment has resulted in the emergence of a serine 882 insertion resistance mutation and treatment failure, it is crucial to identify drug-resistant cytomegalovirus strains and monitor these patients for viral load determination and assessment of their response or lack of response to treatment.
