Study of the ganciclovir resistant UL54 gene mutations in cytomegalovirus infected Kidney and Hematopoietic stem cell transplant recipients

Subject Areas : Virology

leila jalilsani ¹ , Ramin Yaghobi ² , Bita Geramizadeh ³ , َAfsoon Afshari ⁴ , Mohammad hossein Karimi ⁵

1 - PhD student, Department of Microbiology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
2 - Professor, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
3 - Professor, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4 - Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5 - Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Received: 2024-03-10 Accepted : 2024-05-22 Published : 2024-06-09

Keywords: Kidney transplantation, Hematopoietic stem cell transplantation, Cytomegalovirus, Drug resistance,

Abstract :

Background & Objectives: Cytomegalovirus resistance to ganciclovir with specific mutations in the UL54 gene is a factor in treatment failure and disease progression in organ transplant recipients, particularly kidney and hematopoietic stem cell transplant recipients. This study aimed to determine the mutations leading to resistance in the UL54 gene of human cytomegalovirus.

Materials and Methods: In this study, after screening 23 kidney transplant and 2 hematopoietic stem cell transplant recipients with a positive initial CMV test, 6 patients were included in the final study based on the inclusion criteria (at least 2 available follow-ups with positive CMV Real-time PCR results). The UL54 gene was amplified using Nested-PCR, and the PCR products were then sequenced using the Sanger sequencing method. Finch software (version 1.4.0) was used to analyze the sequencing results.

Results: After reviewing the sequencing results, no known mutations were observed in 4 kidney transplant recipients. Also, a serine 882 insertion mutation in the UL54 gene was observed in 1 hematopoietic stem cell transplant recipient. Examination of the phylogenetic tree of the UL54 gene showed that the Iranian isolate ancestrally belongs to 20 reference strains, including the Merlin strain.

Conclusion: Given that the emergence of the serine 882 insertion mutation can weaken the potential for treatment and impair response to ganciclovir, it is very important to monitor the patients in question, determine the viral load, and assess their response or lack of response to treatment.

References:

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