携带A2基因型或D基因型毒株的献血者中隐匿性乙型肝炎病毒的特征分析

Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains.

作者信息

Candotti Daniel, Grabarczyk Piotr, Ghiazza Paola, Roig Roberto, Casamitjana Natalia, Iudicone Paola, Schmidt Michael, Bird Arthur, Crookes Robert, Brojer Ewa, Miceli Michelina, Amiri Azin, Li Chengyao, Allain Jean-Pierre

机构信息

National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK.

出版信息

J Hepatol. 2008 Oct;49(4):537-47. doi: 10.1016/j.jhep.2008.04.017. Epub 2008 Jun 2.

DOI:10.1016/j.jhep.2008.04.017

PMID:18602718

Abstract

BACKGROUND/AIMS: Nucleic acid testing (NAT) for hepatitis B virus (HBV) DNA in blood donations identified occult HBV infection (OBI) as a potential threat to blood safety.

METHODS

A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data.

RESULTS

Ninety-one percent of 77 donor samples of European origin HBV DNA positive but HBV surface antigen (HBsAg) negative were confirmed. Viral load ranged between unquantifiable and 5640 IU/mL (median 25 IU/mL). Fifty-two strains were genotyped (14 HBV(A2) and 38 HBV(D)). Compared to HBsAg+ samples, genotype D was significantly more frequent than genotype A2 in OBIs from Poland or Italy (P<0.04). Amino acid substitutions were concentrated in the immunologically active parts of the Pre-S/S proteins (P<0.0001) affecting both cellular CD8 T-cell epitopes and B-cell neutralizing Major Hydrophilic Region epitopes. Substitutions were more frequent in OBIs than in HBsAg+ strains of both genotype D (P<0.001) and A2 (P<0.01), in OBIs of genotype D than A2 in the 'a' region (P<0.001) but not cellular epitopes, and in anti-HBs+ than anti-HBs- OBIs (P<0.001).

CONCLUSIONS

Results support the hypothesis that humoral and cellular immune pressure on the HBV envelope proteins are major mechanisms generating OBI.

摘要

背景/目的：对献血者血液进行乙肝病毒（HBV）DNA核酸检测（NAT）发现隐匿性HBV感染（OBI）是血液安全的潜在威胁。

方法

开展一项合作研究，以探究欧洲普遍存在的OBI与临床和血清学数据相关的分子基础。

结果

77份欧洲来源的HBV DNA阳性但乙肝表面抗原（HBsAg）阴性的献血者样本中，91%得到确认。病毒载量在不可定量至5640 IU/mL之间（中位数为25 IU/mL）。对52个毒株进行了基因分型（14个HBV（A2）和38个HBV（D））。与HBsAg阳性样本相比，在来自波兰或意大利的OBI中，D基因型明显比A2基因型更常见（P<0.04）。氨基酸替换集中在Pre-S/S蛋白的免疫活性部位（P<0.0001），影响细胞CD8 T细胞表位和B细胞中和主要亲水区表位。在D基因型（P<0.001）和A2基因型（P<0.01）的OBI中，替换比HBsAg阳性毒株更频繁；在“a”区域，D基因型的OBI比A2基因型更频繁（P<0.001），但细胞表位无此情况；在抗-HBs阳性的OBI中比抗-HBs阴性的OBI更频繁（P<0.001）。