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耐药和交叉耐药乙型肝炎病毒突变体的适应性与传染性:为何以及如何进行研究?

Fitness and infectivity of drug-resistant and cross-resistant hepatitis B virus mutants: why and how is it studied?

作者信息

Durantel David

机构信息

INSERM, U871, Lyon, France.

出版信息

Antivir Ther. 2010;15(3 Pt B):521-7. doi: 10.3851/IMP1551.

DOI:10.3851/IMP1551
PMID:20516574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2901352/
Abstract

The emergence of hepatitis B virus (HBV) drug-resistant (and multidrug-resistant) strains during long-term therapy with nucleoside/nucleotide analogues is associated with treatment failure and, therefore, represents a clinical challenge. For clinicians, the close monitoring and management of resistance has become a key issue in clinical practice. For HBV virologists, the understanding of the mechanism of emergence of specific mutant strains in the viral quasispecies during treatment is also an important issue. If a particular viral strain can emerge in the quasispecies within a particular environment, it is probably because its fitness is superior to other strains. The present review focuses on viral fitness as well as viral infectivity, and in particular on technical means that are available to study this viral fitness in vitro and in animal models.

摘要

在核苷/核苷酸类似物长期治疗期间,乙型肝炎病毒(HBV)耐药(及多重耐药)毒株的出现与治疗失败相关,因此是一项临床挑战。对临床医生而言,耐药性的密切监测与管理已成为临床实践中的关键问题。对HBV病毒学家来说,了解治疗期间病毒准种中特定突变毒株的出现机制也是一个重要问题。如果特定病毒毒株能在特定环境下的准种中出现,很可能是因为其适应性优于其他毒株。本综述聚焦于病毒适应性以及病毒感染性,尤其关注可用于在体外和动物模型中研究这种病毒适应性的技术手段。

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本文引用的文献

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A function essential to viral entry underlies the hepatitis B virus "a" determinant.乙肝病毒“a”决定簇的基础是病毒进入所必需的一种功能。
J Virol. 2009 Sep;83(18):9321-8. doi: 10.1128/JVI.00678-09. Epub 2009 Jul 1.
2
Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model.乙肝疫苗对黑猩猩模型中抗病毒药物耐药性乙肝病毒突变体的疗效。
Hepatology. 2009 May;49(5):1483-91. doi: 10.1002/hep.22796.
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Management and prevention of drug resistance in chronic hepatitis B.慢性乙型肝炎耐药性的管理与预防
Liver Int. 2009 Jan;29 Suppl 1:108-15. doi: 10.1111/j.1478-3231.2008.01939.x.
4
Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined immunodeficiency transgenic with urokinase-type plasminogen activator mouse with human hepatocytes.携带人肝细胞的尿激酶型纤溶酶原激活剂转基因严重联合免疫缺陷小鼠中特定乙型肝炎病毒基因型的直接细胞病变效应
Gastroenterology. 2009 Feb;136(2):652-62.e3. doi: 10.1053/j.gastro.2008.10.048. Epub 2008 Oct 29.
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In vitro characterization of viral fitness of therapy-resistant hepatitis B variants.治疗耐药型乙型肝炎变异株病毒适应性的体外特征分析
Gastroenterology. 2009 Jan;136(1):168-176.e2. doi: 10.1053/j.gastro.2008.09.068. Epub 2008 Oct 7.
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N Engl J Med. 2008 Oct 2;359(14):1486-500. doi: 10.1056/NEJMra0801644.
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The human liver-uPA-SCID mouse: a model for the evaluation of antiviral compounds against HBV and HCV.人肝-uPA-SCID小鼠:一种用于评估抗HBV和HCV抗病毒化合物的模型。
Antiviral Res. 2008 Dec;80(3):231-8. doi: 10.1016/j.antiviral.2008.07.006. Epub 2008 Aug 14.
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Initiation of hepatitis B virus genome replication and production of infectious virus following delivery in HepG2 cells by novel recombinant baculovirus vector.新型重组杆状病毒载体在HepG2细胞中递送后启动乙型肝炎病毒基因组复制并产生感染性病毒。
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Antiviral resistance mutations potentiate hepatitis B virus immune evasion through disruption of its surface antigen a determinant.抗病毒耐药性突变通过破坏乙肝病毒表面抗原决定簇来增强其免疫逃避能力。
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The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound.所选的抗乙肝病毒药物对乙肝病毒rtA181T/sW172*突变体具有显性负性分泌缺陷,并改变了病毒反弹的典型模式。
Hepatology. 2008 Jul;48(1):88-98. doi: 10.1002/hep.22295.