比较慢性乙型肝炎患者野生型和拉米夫定耐药性乙型肝炎病

StephenW

Virus Res. 2018 Jul 31. pii: S0168-1702(18)30319-8. doi: 10.1016/j.virusres.2018.07.021. [Epub ahead of print]
Comparison of replication competence of wild-type and lamivudine-resistant hepatitis B virus isolates from a chronic hepatitis B patient.
Zhang Q1, Chen J1, Pan M1, Liu J1, Liu T2, Zhou YH3.
Author information

1
    Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Jiangsu, China.
2
    Department of Transfusion Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China.
3
    Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Jiangsu, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University, Jiangsu, China. Electronic address: [email protected].

Abstract

In lamivudine-refractory chronic hepatitis B (CHB) patients, discontinuation of lamivudine therapy may lead to loss of lamivudine-resistant hepatitis B virus (HBV) and reappearance of wide-type HBV as dominant strains, yet the underlying mechanism remains unclear. In this study, we cloned wide-type and lamivudine-resistant HBV genomes from the sera of a CHB patient who stopped lamivudine therapy after occurrence of resistant virus and determined the biologic properties of the two isolates in hepatoma cell lines. Sequencing reverse transcriptase region of HBV revealed that the patient developed lamivudine-resistant mutations (rtV173 L, rtL180 M, and rtM204 V) 36 months after the start of lamivudine therapy, and lamivudine-resistant mutants reversed to wild-type after the treatment was stopped for 8 months. Our data showed that the wild-type and mutant isolates had similar transcriptional and translational activity. However, comparison of intracellular and released HBV DNA levels showed that replication efficiency of the mutant virus was approximately 50% of wild-type HBV, while the infectivity of released virus was not affected by the lamivudine-resistant mutations. In conclusion, the reversion of lamivudine-resistant mutants to wild-type HBV after discontinuation of lamivudine in hepatitis B patients may be attributed to better replication fitness of wild-type HBV.
KEYWORDS:

hepatitis B virus; lamivudine-resistance; replication fitness; wild-type

PMID:
    30075160
DOI:
    10.1016/j.virusres.2018.07.021

StephenW

病毒资源2018年7月31日.pii：S0168-1702（18）30319-8。 doi：10.1016 / j.virusres.2018.07.021。 [提前打印]
比较慢性乙型肝炎患者野生型和拉米夫定耐药性乙型肝炎病毒分离株的复制能力。
Zhang Q1，Chen J1，Pan M1，Liu J1，Liu T2，Zhou YH3。
作者信息

1
    南京大学医学院南京鼓楼医院检验科，江苏省分子医学重点实验室，江苏南京
2
    南京大学医学院南京鼓楼医院输血医学科，江苏
3
    南京大学医学院南京鼓楼医院检验科，江苏省分子医学重点实验室，江苏南京;南京医科大学南京鼓楼医院感染科，江苏电子地址：[email protected]。

抽象

在拉米夫定难治性慢性乙型肝炎（CHB）患者中，停用拉米夫定治疗可能导致拉米夫定耐药性乙型肝炎病毒（HBV）的丧失和广泛型HBV再次出现为显性菌株，但其潜在机制尚不清楚。在这项研究中，我们从CHB患者的血清中克隆了宽型和拉米夫定耐药的HBV基因组，该患者在出现耐药病毒后停止拉米夫定治疗，并确定了两种分离株在肝癌细胞系中的生物学特性。对HBV的逆转录酶区域进行测序显示，患者在拉米夫定治疗开始36个月后出现拉米夫定耐药突变（rtV173L，rtL180M和rtM204V），拉米夫定耐药突变体在治疗停止后逆转为野生型为期8个月。我们的数据显示野生型和突变型分离株具有相似的转录和翻译活性。然而，细胞内和释放的HBV DNA水平的比较显示突变病毒的复制效率约为野生型HBV的50％，而释放的病毒的感染性不受拉米夫定抗性突变的影响。总之，在乙型肝炎患者中停用拉米夫定后拉米夫定耐药突变体向野生型HBV的逆转可归因于野生型HBV的更好的复制适应性。
关键词：

乙型肝炎病毒;拉米夫定抗性;复制健身;野生型

结论：
    30075160
DOI：
    10.1016 / j.virusres.2018.07.021

默然10

其实想起王主任的拉米使用情况。