Nature子刊：美学者发表乙肝药物相关论文

2017年6月26日，国际学术权威刊物自然出版集团旗下子刊《Nature Biomedical Engineering》杂志在线发表了英国利兹大学Peter G. Stockley研究员、Neil A. Ranson研究员和约克大学Reidun Twarock研究员合作的一篇研究论文，研究发现了乙型肝炎病毒产生作用的关键机制，有助医学界未来开发出治疗疾病的有效药物。

乙肝是由乙型肝炎病毒造成的可能威胁生命的肝脏感染，可造成慢性感染，患者死于肝硬化和肝癌的风险很高。虽然人们可以通过接种乙肝疫苗进行预防，但目前还没有治疗乙肝的药物。

研究人员领衔的团队深入分析了乙肝病毒。他们发现，这种病毒的遗传物质中存在一种“组合代码”，能够让病毒形成一个保护层，从而在其中复制出新的具感染性病毒分子。进一步分析显示，乙肝病毒核糖核酸产生的信号能吸引病毒蛋白，还能使病毒蛋白按一种特定的几何形态进行组合。

据研究人员介绍，这一机制好比自行车的链条，如果链条没有被拼接到链轮上就会缠在一起，无法发挥正常作用，但如果正确地组合在一起，就能把脚踏板与车轮联动起来，自行车才能正常运行。

原文摘要：

Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA. The RNA oligos do not interact with preformed RNA-free VLPs, so their effects must occur during particle assembly. Asymmetric cryo-electron microscopy reconstruction of the T = 4 VLPs assembled in the presence of one of the RNAs reveals a unique internal feature connected to the main core protein shell via lobes of density. Biophysical assays suggest that this is a complex involving several RNA oligos interacting with the C-terminal arginine-rich domains of core protein. These core protein–RNA contacts may play one or more roles in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for nucleocapsid assembly.