台湾地区巨细胞病毒 UL97 和 UL54 变异株的分子流行病学研究。

Molecular Epidemiology of Cytomegalovirus UL97 and UL54 variants in Taiwan.

机构信息

Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.

Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

出版信息

J Microbiol Immunol Infect. 2021 Oct;54(5):971-978. doi: 10.1016/j.jmii.2021.01.007. Epub 2021 Feb 17.

DOI:10.1016/j.jmii.2021.01.007

PMID:33632621

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

巨细胞病毒 (CMV) 感染的抗病毒耐药性与 CMV UL54 和 UL97 基因区域的突变有关，这在免疫功能低下的患者中是一个严重的问题。然而，台湾的 UL54 和 UL97 的分子流行病学尚不清楚。

方法

我们对 2016 年 1 月至 12 月期间在台湾的两家三级医院和一家地区医院患有 CMV 感染的患者进行了回顾性研究。CMV DNA 血症通过升高的 CMV DNA 滴度来确认。然后通过 PCR 扩增 UL54 和 UL97 突变区域并进行测序。

结果

在 729 例 CMV 综合征患者中，有 112 例 CMV DNA 血症患者入选。在 UL54 中发现了 12 种新的变异（P342S、S384F、K434R、S673F、T754M、R778H、C814S、M827I、G878E、S880L、E888K 和 S976N）和 UL97 中的一个新变异（M615T）。在 4 名患者（3.6%）中发现了 UL97 抗病毒耐药突变（L595S、M460I 和 M460V）。在耐药株中，突变事件发生在治疗后 83-150 天，这些患者也出现了耐药性。观察到以下高频变异：UL97 中的 D605E 和 A885T、UL54 中的 N898D、V355A、N685S 和 A688V。

结论

结果表明，在有临床 CMV 感染症状的患者中，CMV DNA 血症的阳性率为 15.3%（112/729）。CMV DNA 血症患者中抗病毒耐药性 CMV 株的比例为 3.6%。鉴于本研究中 UL54 和 UL97 患者的多态性发生率信息，建议对免疫功能低下的难治性 CMV 感染人群进行 UL54 和 UL97 的遗传谱测定。