Native hepatitis B virions and capsids visualized by electron cryornicroscopy
Native hepatitis B virions and capsids visualized by electron cryornicroscopy
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DOI：
10.1016/j.molcel.2006.04.025
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发表时间：
2006-06-23
期刊：
影响因子：
16
通讯作者：
Yeager, Mark
中科院分区：
文献类型：
--
作者：
Dryden, Kelly A.;Wieland, Stefan F.;Yeager, Mark
B型肝炎病毒（HBV）感染超过3.5亿人，其中每年将有100万人死亡。感染性病毒粒子是含有病毒聚合酶和双链DNA基因组的包膜衣壳。由表达的核心蛋白体外组装的衣壳的结构已经被深入研究。然而，对感染细胞中天然衣壳的结构和组装知之甚少，对成熟病毒体的结构更是知之甚少。我们使用冷冻电镜（cryo-EM）和图像分析来检查从患者血清中分离的HBV病毒体（Dane颗粒）和从转基因小鼠肝脏中分离的HBV DNA阳性和阴性衣壳。这两种类型的衣壳作为二十面体粒子组装从以前的图像重建的衣壳难以区分。同样，病毒体含有T=3或T=4二十面体对称的衣壳。从脂质包膜延伸的突起归因于表面糖蛋白。它们的堆积出乎意料地是二十面体的，但符合有序晶格。这些结构特征将HBV与其他包膜病毒区分开来。
Hepatitis B virus (HBV) infects more than 350 million people, of which one million will die every year. The infectious virion is an enveloped capsid containing the viral polymerase and double-stranded DNA genome. The structure of the capsid assembled in vitro from expressed core protein has been studied intensively. However, little is known about the structure and assembly of native capsids present in infected cells, and even less is known about the structure of mature virions. We used electron cryomicroscopy (cryo-EM) and image analysis to examine HBV virions (Dane particles) isolated from patient serum and capsids positive and negative for HBV DNA isolated from the livers of transgenic mice. Both types of capsids assembled as icosahedral particles indistinguishable from previous image reconstructions of capsids. Likewise, the virions contained capsids with either T=3 or T=4 icosahedral symmetry. Projections extending from the lipid envelope were attributed to surface glycoproteins. Their packing was unexpectedly nonicosahedral but conformed to an ordered lattice. These structural features distinguish HBV from other enveloped viruses.