Identification of a novel hepatitis B virus precore/core deletion mutant in HIV/hepatitis B virus co-infected individuals.
Identification of a novel hepatitis B virus precore/core deletion mutant in HIV/hepatitis B virus co-infected individuals.
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HIV/乙型肝炎病毒共感染个体中新型乙型肝炎病毒前核心/核心缺失突变体的鉴定。
DOI：
10.1097/qad.0b013e32826fb305
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Locarnini,StephenA
中科院分区：
文献类型：
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作者：
Revill,PeterA;Littlejohn,Margaret;Ayres,Anna;Yuen,Lilly;Colledge,Danni;Bartholomeusz,Angeline;Sasaduesz,Joe;Lewin,SharonR;Dore,GregoryJ;Matthews,GailV;Thio,ChloeL;Locarnini,StephenA
目的：尽管 HAART 改善了大多数 HIV 感染者的健康状况，但肝功能衰竭已成为乙型肝炎病毒 (HBV) 合并感染者发病和死亡的主要原因。在乙型肝炎病毒单一感染个体中，核心缺失突变体与更严重的肝病相关。由于 HIV 加速 HBV 肝病进展，我们假设 HIV-HBV 共感染个体的核心突变（包括缺失）频率增加。为了检验这一假设，我们分析了抗病毒治疗前和抗病毒治疗期间患者的 HBV DNA 基因组长度序列。背景：前瞻性 HIV/HBV 合并感染队列研究。方法：在拉米夫定治疗开始前和治疗 9 至 74 个月后，通过 PCR 从 10 名 HIV/HBV 合并感染者和 5 名 HBV 单一感染者的血清样本中扩增基因组长度 HBV DNA。对完整基因组进行了测序，为了进一步分析一些突变，在另外的 HIV/HBV 共同感染者和 HBV 单一感染者中确定了它们的频率。 结果：在 HBV 前核心和重叠核心基因中发现了一种新的 –1G 突变，该突变截断了推导的前核心/核心蛋白。突变基因组是一些 HIV/HBV 合并感染个体中的优势物种，并且在 HIV/HBV 合并感染个体中比 HBV 单一感染个体更普遍。该突变还与 HIV/HBV 共感染个体的高 HBV DNA 浓度相关。在核心/前核心和聚合酶基因和调控区中还发现了其他突变。结论：HBV 核心和前核心基因的突变可能与 HIV/HBV 共感染个体的疾病发病机制有关。
Objectives:Although HAART has resulted in improved health outcomes for most HIV-infected individuals, liver failure has emerged as a major cause of morbidity and mortality in people co-infected with hepatitis B virus (HBV). In HBV mono-infected individuals, core deletion mutants are associated with more aggressive liver disease. As HIV accelerates HBV liver disease progression, we hypothesized that HIV-HBV co-infected individuals have increased frequency of core mutations including deletions. To test this hypothesis, we have analysed genome-length sequences of HBV DNA from patients both prior to and during antiviral therapy.Setting:Prospective HIV/HBV co-infected cohort study.Methods:Genomic length HBV DNA was amplified by PCR from the serum samples of ten HIV/HBV co-infected individuals and five HBV mono-infected individuals prior to the commencement of lamivudine therapy and again after nine to 74 months of treatment. The complete genomes were sequenced and in order to further analyse some mutations, their frequency was determined in additional HIV/HBV co-infected and HBV mono-infected individuals.Results:A novel–1G mutation was identified in the HBV precore and overlapping core genes that truncated the deduced precore/core proteins. The mutant genome was the dominant species in some HIV/HBV co-infected individuals and was more prevalent in HIV/HBV co-infected individuals than HBV mono-infected individuals. The mutation was also associated with high HBV DNA concentrations in HIV/HBV co-infected individuals. Additional mutations were identified in the core/precore and polymerase genes and regulatory regions.Conclusion:Mutations in the HBV core and precore genes may be contributing to disease pathogenesis in HIV/HBV co-infected individuals.