尽管埃塞俄比亚乙型肝炎病毒高度流行，但德尔塔病毒的进化枝同质性和低感染率。

Clade homogeneity and low rate of delta virus despite hyperendemicity of hepatitis B virus in Ethiopia.

作者信息

Belyhun Yeshambel, Liebert Uwe Gerd, Maier Melanie

机构信息

Institute of Virology, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

出版信息

Virol J. 2017 Sep 12;14(1):176. doi: 10.1186/s12985-017-0844-z.

DOI:10.1186/s12985-017-0844-z

PMID:28899424

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5596854/

Abstract

BACKGROUND

Although hepatitis B virus (HBV) is hyperendemic and heterogeneous in its genetic diversity in Ethiopia, little is known about hepatitis D virus (HDV) circulating genotypes and molecular diversity.

METHODS

A total of 321 hepatitis B surface antigen (HBsAg) positives (125 HIV co-infected, 102 liver disease patients and 94 blood donors) were screened for anti-HDV antibody. The anti-HDV positive sera were subjected to Real time PCR for HDV-RNA confirmation. The non coding genome region (spanning from 467 to 834 nucleotides) commonly used for HDV genotyping as well as complete HDV genome were sequenced for genotyping and molecular analysis.

RESULTS

The anti-HDV antibody was found to be 3.2% (3) in blood donors, 8.0% (10) in HIV co-infected individuals and 12.7% (13) in liver disease patients. None of the HIV co-infected patients who revealed HBV lamivudine (3TC) resistance at tyrosine-methionine/isoleucine-aspartate-aspartate (YM(I)DD) reverse transcriptase (RT) motif with concomitant vaccine escape gene mutants was positive for anti-HDV antibody. The HDV viremia rate was 33.3%, 30.0% and 23.1% in respect to the above study groups. All the six isolates sequenced were phylogenetically classified as HDV genotype 1 (HDV-1) and grouped into two monophyletic clusters. Amino acid (aa) residues analysis of clathrin heavy chain (CHC) domain and the isoprenylation signal site (Py) at 19 carboxyl (C)-terminal amino acids (aa 196-214) and the HDV RNA binding domain (aa 79-107) were highly conserved and showed a very little nucleotide variations. All the sequenced isolates showed serine at amino acid position 202. The RNA editing targets of the anti-genomic HDV RNA (nt1012) and its corresponding genomic RNA (nt 580) showed nucleotides A and C, respectively.

CONCLUSIONS

The low seroprevalence and viraemic rates of HDV in particular during HIV-confection might be highly affected by HBV drug resistance selected HBsAg mutant variants in this setting, although HDV-1 sequences analysis revealed clade homogeneity and highly conserved structural and functional domains. Thus, the potential role of HBV drug resistance associated polymerase mutations and concomitant HBsAg protein variability on HDV viral assembly, secretion and infectivity needs further investigation.

摘要

背景

尽管乙型肝炎病毒（HBV）在埃塞俄比亚高度流行且基因多样性存在异质性，但对于丁型肝炎病毒（HDV）的流行基因型和分子多样性知之甚少。

方法

对总共321例乙型肝炎表面抗原（HBsAg）阳性者（125例合并感染HIV者、102例肝病患者和94例献血者）进行抗HDV抗体筛查。抗HDV阳性血清进行实时PCR以确认HDV-RNA。对常用于HDV基因分型的非编码基因组区域（跨度为467至834个核苷酸）以及完整的HDV基因组进行测序以进行基因分型和分子分析。

结果

抗HDV抗体在献血者中的检出率为3.2%（3例），在合并感染HIV者中为8.0%（10例），在肝病患者中为12.7%（13例）。在酪氨酸-甲硫氨酸/异亮氨酸-天冬氨酸-天冬氨酸（YM(I)DD）逆转录酶（RT）基序处显示出HBV拉米夫定（3TC）耐药且伴有疫苗逃逸基因突变的合并感染HIV患者中，无一例抗HDV抗体呈阳性。上述研究组的HDV病毒血症率分别为33.3%、30.0%和23.1%。所有测序的6株分离株在系统发育上均被分类为HDV基因型1（HDV-1），并分为两个单系簇。网格蛋白重链（CHC）结构域以及19个羧基（C）末端氨基酸（第196至214位氨基酸）处的异戊二烯化信号位点（Py）和HDV RNA结合结构域（第79至107位氨基酸）的氨基酸（aa）残基分析高度保守，核苷酸变异很少。所有测序的分离株在第202位氨基酸处均为丝氨酸。抗基因组HDV RNA（nt1012）及其相应的基因组RNA（nt 580）的RNA编辑靶点分别显示核苷酸A和C。

结论

HDV的低血清流行率和病毒血症率，尤其是在HIV感染期间，可能在这种情况下受到HBV耐药性选择的HBsAg突变变体的高度影响，尽管HDV-1序列分析显示进化枝同质性以及高度保守的结构和功能结构域。因此，HBV耐药相关聚合酶突变以及伴随的HBsAg蛋白变异性对HDV病毒组装、分泌和感染性的潜在作用需要进一步研究。