Molecular Epidemiology of Cytomegalovirus UL97 and UL54 variants in Taiwan

The antiviral resistance of cytomegalovirus (CMV) infections is associated with mutations in the CMV UL54 and UL97 gene regions and is a serious problem in immunocompromised patients. However, the molecular epidemiology of UL54 and UL97 in Taiwan is unclear.

We conducted a retrospective study of patients with CMV infections between January and December 2016 in two tertiary hospitals, one regional hospital in Taiwan. CMV DNAemia was confirmed by elevated CMV DNA titers. Then the regions of the UL54 and UL97 mutations were amplified by PCR and sequenced.

Of 729 patients with CMV syndrome, 112 CMV DNAemia patients were enrolled. Twelve novel variants in UL54 (P342S, S384F, K434R, S673F, T754M, R778H, C814S, M827I, G878E, S880L, E888K, and S976N) and one novel variant in UL97 (M615T) were discovered. UL97 antiviral resistance mutations (L595S, M460I, and M460V) were found in four patients (3.6%). In the drug resistance strains, the mutation events occurred after 83-150 days of therapy, and drug resistance was also observed in these patients. The following high frequency variants were observed: D605E in UL97 and A885T, N898D, V355A, N685S, and A688V in UL54.

The results demonstrate that the positive rate of CMV DNAemia was 15.3% (112/729) among the patients with clinical CMV infection symptoms. The proportion of antiviral resistance CMV strains within CMV DNAemia patients was 3.6%. With the information of polymorphism incidence in the UL54 and UL97 patients from our study, determination of the genetic profile of UL54 and UL97 among immunocompromised populations with refractory CMV infection is recommended.