乙型肝炎病毒核心和e抗原免疫复合物的结构建议多点抑

StephenW

Structure. 2018 Jul 17. pii: S0969-2126(18)30244-2. doi: 10.1016/j.str.2018.06.012. [Epub ahead of print]
Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition.
Eren E1, Watts NR2, Dearborn AD2, Palmer IW2, Kaufman JD2, Steven AC1, Wingfield PT3.
Author information

1
    Laboratory of Structural Biology Research, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
2
    Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
3
    Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].

Abstract

Hepatitis B virus (HBV) is the leading cause of liver disease worldwide. While an adequate vaccine is available, current treatment options are limited, not highly effective, and associated with adverse effects, encouraging the development of alternative therapeutics. The HBV core gene encodes two different proteins: core, which forms the viral nucleocapsid, and pre-core, which serves as an immune modulator with multiple points of action. The two proteins mostly have the same sequence, although they differ at their N and C termini and in their dimeric arrangements. Previously, we engineered two human-framework antibody fragments (Fab/scFv) with nano- to picomolar affinities for both proteins. Here, by means of X-ray crystallography, analytical ultracentrifugation, and electron microscopy, we demonstrate that the antibodies have non-overlapping epitopes and effectively block biologically important assemblies of both proteins. These properties, together with the anticipated high tolerability and long half-lives of the antibodies, make them promising therapeutics.
KEYWORDS:

Fab; HBcAg; HBeAg; antibody fragments; capsid assembly; epitopes; hepatitis B virus; nucleocapsid; scFv; therapeutics

PMID:
    30100358
DOI:
    10.1016/j.str.2018.06.012

StephenW

结构体。 2018年7月17日.pii：S0969-2126（18）30244-2。 doi：10.1016 / j.str.2018.06.012。 [提前打印]
乙型肝炎病毒核心和电子抗原免疫复合物的结构建议多点抑制。
Eren E1，Watts NR2，Dearborn AD2，Palmer IW2，Kaufman JD2，Steven AC1，Wingfield PT3。
作者信息

1
    结构生物学研究实验室，NIAMS，国立卫生研究院，贝塞斯达，MD 20892，USA。
2
    蛋白质表达实验室，NIAMS，National Institutes of Health，Bethesda，MD 20892，USA。
3
    蛋白质表达实验室，NIAMS，National Institutes of Health，Bethesda，MD 20892，USA。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）是全球肝病的主要原因。虽然可获得足够的疫苗，但目前的治疗方案有限，不是非常有效，并且与不良反应有关，因此鼓励开发替代疗法。 HBV核心基因编码两种不同的蛋白质：核心，形成病毒核衣壳，和核心，作为具有多个作用点的免疫调节剂。这两种蛋白质大多数具有相同的序列，尽管它们的N和C末端以及它们的二聚体排列不同。以前，我们设计了两种人体框架抗体片段（Fab / scFv），对两种蛋白质都具有纳米到皮摩尔的亲和力。在这里，通过X射线晶体学，分析超速离心和电子显微镜，我们证明抗体具有非重叠的表位并有效地阻断两种蛋白质的生物学上重要的组装。这些特性以及预期的高耐受性和抗体的长半衰期使其成为有前途的治疗方法。
关键词：

晶圆厂;核心抗原;大三阳;抗体片段;衣壳组装;表位;乙型肝炎病毒;核衣壳; scFv的;疗法

结论：
    30100358
DOI：
    10.1016 / j.str.2018.06.012