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东帝汶献血者中乙型肝炎病毒的基因型、亚型及基因变异性

Genotypes, subtypes, and genetic variability of hepatitis B virus from blood donors in Timor-Leste.

作者信息

da Silva Hendriketa, Amin Mochamad, Soares Januari, Soares Miguel, Malik Hitler, Ximenes Antonio, Bela Maria, Fernandes Bernadino

机构信息

Postdoctoral Fellowship Program, Universitas Airlangga, Surabaya, Indonesia.

Postgraduation and Research Program, Faculty of Medicine and Health Sciences, Universidade Nacional Timor-Loro sae, Dili, Timor-Leste.

出版信息

Arch Virol. 2025 May 1;170(6):119. doi: 10.1007/s00705-025-06305-6.

DOI:10.1007/s00705-025-06305-6
PMID:40310552
Abstract

Timor-Leste experiences high hepatitis B endemicity; however, information about hepatitis B virus (HBV) variants in Timor-Leste is still limited. In this study, we determined genotypes and subtypes and identified mutations in the surface (S), polymerase (P), basal core promoter (BCP), precore (PC), and core (C) genes of HBV isolates from blood donors in Timor-Leste. Sera were examined using serological tests and PCR sequencing. Out of 127 sera tested, 38 (30%) were positive for the hepatitis B S antigen (HBsAg). Thirty-eight sequences of the S and P genes, 22 sequences of the BCP and PC regions, and 23 sequences of C genes were determined and analyzed. The most common genotype/subtype was C/adrq+, followed by B/ayw1, B/adw2, and C/adw2. Several mutations in the S protein that are associated with vaccine escape were identified in samples of genotype C (I110L, S113T, T126I, T143S, Y161F) and B (K122R), some of which might have been from vaccinated individuals. None of the healthy carriers had taken anti-HBV drugs, but one was infected with a virus with a mutation in the P gene associated with anti-HBV drug resistance (Y141F). The mutations A1762T and G1764A in BCP were detected in 18.1-22.7% of the samples. In the PC region, the mutation C1858T was the most frequent, followed by G1896A and G1899A. In the C gene, 13 mutations (P5T, T67N, E77Q, P79Q/A, E83D, V91T, I97L/F, L116I, and P130I/P/T) associated with severe liver disease were identified. Viruses obtained from four healthy carriers who were later found to have died of hepatocellular carcinoma also showed those mutations. In conclusion, among blood donors in Timor-Leste, HBV genotype/subtype C/adrq+ and several mutations in the S and C genes were prevalent. Routine implementation of a national immunization program and monitoring of disease progression in healthy carriers should be considered.

摘要

东帝汶乙型肝炎流行率很高;然而,关于东帝汶乙型肝炎病毒(HBV)变异株的信息仍然有限。在本研究中,我们确定了基因型和亚型,并鉴定了来自东帝汶献血者的HBV分离株表面(S)、聚合酶(P)、核心启动子(BCP)、前核心(PC)和核心(C)基因中的突变。使用血清学检测和PCR测序对血清进行检测。在127份检测的血清中,38份(30%)乙型肝炎表面抗原(HBsAg)呈阳性。测定并分析了38个S和P基因序列、22个BCP和PC区域序列以及23个C基因序列。最常见的基因型/亚型是C/adrq+,其次是B/ayw1、B/adw2和C/adw2。在C基因型(I110L、S113T、T126I、T143S、Y161F)和B基因型(K122R)样本中鉴定出了一些与疫苗逃逸相关的S蛋白突变,其中一些可能来自接种过疫苗的个体。所有健康携带者均未服用抗HBV药物,但有1人感染了一种P基因发生与抗HBV耐药相关突变(Y141F)的病毒。BCP区域中的A1762T和G1764A突变在18.1%至22.7%的样本中被检测到。在PC区域,C1858T突变最为常见,其次是G1896A和G1899A。在C基因中,鉴定出13个与严重肝病相关的突变(P5T、T67N、E77Q、P79Q/A、E83D、V91T、I97L/F、L116I和P130I/P/T)。从4名后来被发现死于肝细胞癌的健康携带者身上获得的病毒也显示出这些突变。总之,在东帝汶的献血者中,HBV基因型/亚型C/adrq+以及S和C基因中的一些突变很普遍。应考虑常规实施国家免疫规划并监测健康携带者的疾病进展。

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