隐匿性乙型肝炎患者病毒全长基因组分析

Analysis on the full-length genomes of hepatitis B virus isolated from occult hepatitis B patients

目的了解隐匿性乙型肝炎(OBI)患者病毒全长基因组,探讨形成OBI的可能病毒学原因。方法用病毒核酸抽提试剂盒提取7例OBI患者核酸,用高灵敏度巢氏PCR扩增HBV全长基因组,对扩增产物进行测序,将测得序列与GenBank中的标准序列进行比对,分析氨基酸变异情况。结果OBI患者病毒载量较低,抗-HBc阳性有6份,S区和C区突变主要存在于B细胞、Th和CTL表位上,如P47L、F22L、D44N、P79Q等位点;X区和P区也存在部分突变。结论HBV全长基因组S、C、X区等多个关键性位点的突变导致HBV抗原性改变及病毒粒子分泌减弱,从而形成OBI。

Objective To investigate the full-length genomes of HBV in patients with occult hepatitis B infection (OBI), and to explore the possible virological causes of OBI. Methods Nucleic acids from 7 OBI individuals were extracted by viral nucleic acid extraction kit. The whole genome of HBV was amplified by high sensitive nested PCR. The amplified products were sequenced and compared with the standard sequences in GenBank, so as to analyze the amino acid variation. Results All the OBI patients had low viral load, among whom 6 cases were anti-HBc positive. There were many point mutations on the epitopes of B cells, helper T cells and cytotoxic T lymphocytes in S and C regions, such as P47L, F22L, D44N and P79Q mutations. Some point mutations existed in X and P regions. Conclusions Mutations at multiple key sites in S, C and X regions lead to the antigenicity change of HBV and the decrease of virion secretion, thus leads to OBI.