紧密聚集的戊型肝炎病毒 1a 基因型与孟加拉国的地方性和暴发感染有关。
A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
机构信息
Oxford University Clinical Research Unit, Wellcome Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh.
出版信息
PLoS One. 2021 Jul 22;16(7):e0255054. doi: 10.1371/journal.pone.0255054. eCollection 2021.
BACKGROUND
Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains.
METHODS
We analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined.
RESULTS
92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively.
CONCLUSION
Strains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.
背景
戊型肝炎病毒（HEV）感染在孟加拉国流行，偶尔会爆发疫情。目前，人们对地方性和爆发性 HEV 株的分子特征和发病机制了解甚少。本研究比较了地方性 HEV 株与爆发性 HEV 株的遗传相关性和与毒力相关的突变。
方法
我们系统地分析了 2013 年 8 月至 2015 年 6 月在孟加拉国达卡的 Bangabandhu Sheikh Mujib 医科大学就诊的 HEV 免疫球蛋白 M（IgM）阳性患者的血清样本。HEV RNA 阳性样本进行全基因组测序。通过系统进化分析确定株的基因型和亚型。确定与毒力相关的突变，如急性病毒性肝炎（AVH）、暴发性肝衰竭（FHF）、慢性肝炎、利巴韦林治疗失败（RTF）、B 细胞和 T 细胞中和表位。
结果
研究了 92 份 HEV 免疫球蛋白 M（IgM）抗体阳性血浆样本（2013-2014 年 43 份，2014-2015 年 49 份）。77.1%（70/92）的样本 HEV RNA 阳性。从 54.2%（38/70）的株中获得了 279bp 开放阅读框（ORF）2 和 ORF 3 序列。在 38 株中，有 21 株获得了全基因组序列（WGS）。在 38 个（279bp）序列的系统进化分析中，所有 HEV 序列均属于基因型 1 和亚型 1a。对 21 株 HEV WGS 的进一步系统进化分析表明，孟加拉国的 HEV 序列与邻国的基因型 1a 序列聚集在一起。在基因型 1a 聚类中，孟加拉国的 HEV 株与 2010 年来自孟加拉国北部的 HEV 爆发株形成了一个单独的聚类。80.9%至 100%的株具有与 AVH、FHF 和 RTF 相关的 A317T、T735I、L1120I、L1110F、P259S、V1479I、G1634K 突变。T 细胞识别表位 T3、T5、T7 的突变分别在 76.1%、100%和 100%的株中观察到。
结论
孟加拉国的 HEV 基因型 1a 占主导地位，与地方性和爆发性 HEV 感染有关。孟加拉国的 HEV 分离株具有高毒力相关突变和改变 B 细胞和 T 细胞表位抗原性的突变。
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