박, Park, 허, Hur, 성, Sung, 최, Choi, 김, and Kim: Antiviral Resistance in Human Cytomegalovirus Due to UL54 Mutations Without UL97 Mutations

Kuenyoul Park1Kyu-Hwa Hur2Heungsup Sung1*Sang-Ho Choi3Mi-Na Kim1

1Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Laboratory Medicine, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, Korea
3Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

*Corresponding author: Tel: +82-2-3010-4499, Fax: +82-2-478-0884, E-mail: sung@amc.seoul.kr


Background: The concurrent detection of human cytomegalovirus (CMV) with UL97 and UL54 mutations is crucial for prescribing adequate antiviral treatment when drug-resistant CMV infection is suspected. We investigated the frequency of resistance-conferring mutations among patients with persistent or recurrent CMV infection and further reviewed the subgroup with UL54 mutations without UL97 mutations.

Methods: Patients with persistent or recurrent CMV infection after 4 weeks of treatment with ganciclovir or foscarnet were consecutively enrolled between November 2012 and May 2019. The direct sequencing of UL97 and UL54 was performed to detect resistance mutations in CMV.

Results: A total of 101 sequencing datasets were obtained from 65 enrolled patients. CMV UL97 and UL54 mutations were detected in 15.4% (10/65) and 9% (6/65) of patients, respectively. The CMV retrieved from two patients (3%) had mutations in both genes. Four patients with CMV UL54 mutations alone had a history of haploidentical peripheral blood stem cell transplantation, and foscarnet was administered for over 4 weeks to these patients; 21.5% of patients had suspected resistant CMV infection with either UL97 or UL54 mutations.

Conclusion: In this study, CMV UL54 mutations but not UL97 mutations were found in patients subjected to prolonged foscarnet administration for CMV disease.


Figures & Tables


Fig. 1. CMV kinetics of four cases with UL54 mutations alone (Patients #6, #11, #14, #19). Bar graph indicates the duration of antiviral drug administration. Blue arrows indicate the specimen dates of CMV viruses with specified UL54 mutations. CMV, cytomegalovirus; PBSCT, peripheral blood stem cell transplantation; CSF, cerebrospinal fluid