A preliminary study on the UL97 gene of cytomegalovirus isolated from patients suspected of ganciclovir resistance in Sri Lanka

Abstract

Background: Human cytomegalovirus (HCMV) is an opportunistic virus causing infections in immunocompromised patients. The widespread use of ganciclovir to treat CMV infections has led to the development of ganciclovir resistance. To date, no studies have been reported in Sri Lanka on mutations in viral genes detected from CMV identified by PCR. No Sri Lankan studies have been reported to date of ganciclovir resistance associated CMV gene mutations. Objective: To screen the CMV UL97 gene identified in a cohort of patients who did not respond to ganciclovir for resistance conferring mutations. Methodology: A retrospective study was carried out on suspected ganciclovir resistant patients who had static or increased levels of CMV viraemia treated with ganciclovir for 2-3 weeks to determine mutations of UL97 gene. DNA of CMV was extracted; Codons 439 – 645 of the UL97 gene was amplified by PCR only from patients who did not respond to ganciclovir and two fragments of 354bp (1317-1671) and 285bp (1650-1935) were sequenced. Results: Twelve of the 340 patients with CMV infection had static or increased levels of CMV viraemia despite being treated with ganciclovir for 2-3 weeks. No mutation was found in the UL97 gene detected from the 12 patients which could confer ganciclovir resistance. However, there was an incidental finding of a single nucleotide change from thymine to cytosine at the 1368 nucleotide position of the UL97 gene which was detected in all 12 patients. Conclusion: No mutation was found in the UL97 gene from CMV patients in this preliminary study which could confer ganciclovir resistance. UL54 gene of CMV should be considered in addition to UL97 gene in future studies as mutations reported in both genes are known to contribute to ganciclovir resistance.

Keywords

• human cytomegalovirus
• ganciclovir resistance
• ul97 gene