Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, Jiangsu province, China.
Sci Rep. 2018 Jan 29;8(1):1738. doi: 10.1038/s41598-018-20137-2.
Orally-transmitted viruses have evolved in a way to resist the extreme conditions of the host's gastrointestinal environment, especially the proteolysis of their structural proteins. However, the mechanisms allowing these viruses to survive these harsh conditions remain unclear. Hepatitis E virus (HEV) is an orally-transmitted human pathogen. Its capsid protein contains three domains S, P1 and P2. The latter forms a homodimer protruding from the virus shell, making it the most exposed part. By combining biochemical and computational methods, we found the trypsin digestion sites to be highly conserved among the HEV strains. Furthermore, the constructs of the HEV capsid protein that contain an extended P2 domain were digested within the extensions leaving the P2 domain intact. The trypsinization seems to occur in three possible double cleavages at R451-R619, R460-R619 or R460-R631.The dimerization disrupts the trypsin action at three main sites in the P2 domain R542, K544 and K554. These sites are very exposed in the monomeric P2 domain constructs which makes the monomeric forms very susceptible to trypsin action. Therefore, we believe that dimerization is a structural feature that has been selected by the evolutionary forces to render the HEV capsid protein resistant to the host's proteases; an evolutionary feature that could be common to some other (if not all) orally-transmitted viruses.
经口传播的病毒已经进化出了抵抗宿主胃肠道环境极端条件的能力，尤其是抵抗其结构蛋白的蛋白水解作用。然而，这些病毒能够在这些恶劣条件下生存的机制仍不清楚。戊型肝炎病毒（HEV）是一种经口传播的人类病原体。其衣壳蛋白包含三个结构域 S、P1 和 P2。后者形成一个从病毒壳中突出的同源二聚体，使其成为最暴露的部分。通过结合生化和计算方法，我们发现 HEV 株之间的胰蛋白酶消化位点高度保守。此外，包含扩展 P2 结构域的 HEV 衣壳蛋白构建体在延伸部分被消化，而 P2 结构域保持完整。胰蛋白酶似乎可以在 R451-R619、R460-R619 或 R460-R631 三个可能的双切割位点发生。二聚化破坏了 P2 结构域中三个主要位点的胰蛋白酶作用，即 R542、K544 和 K554。这些位点在单体 P2 结构域构建体中非常暴露，这使得单体形式非常容易受到胰蛋白酶的作用。因此，我们认为二聚化是一种结构特征，它已经被进化力量选择，使 HEV 衣壳蛋白能够抵抗宿主的蛋白酶；这种进化特征可能在其他（如果不是全部）经口传播的病毒中是共同存在的。
