Xu K, Yu X, Kong Y, Wang Y, Li Z
Shanghai Institute of Biochemistry, Chinese Academy of Sciences.
Sci China B. 1995 Mar;38(3):320-7.
Four pairs of HBV surface antigen genes, in which the preS region was partially deleted, were constructed by the polymerase chain reaction (PCR). The comparison of the levels of the expression in mammalian cells of these genes and the ones constructed before, and the properties of these gene products showed that the missing of a part of the preS region did not affect the overall spatial structure of the S region and the surface localization of the preS region. The removal of the preS1 retention sequence (a. a. 2-19) alleviated significantly the shelter of the major antigenic determinants in the S region by the preS sequence. It was found that the long preS region seriously impaired the secretion of the surface antigen proteins from mammalian cells. In addition to the previously reported preS1 retention sequence, the preS1 sequence (a.a. 48-65) may also inhibit the secretion of the surface antigen proteins, whereas the preS2 region exerts no major influence on the retention of the large surface antigen protein. One of the expressed surface antigen proteins, in which the preS1 sequence (a.a. 21-47) and the S region were directly fused, deserves further study and may be developed into a new HBV vaccine which contains the preS1 binding site for hepatocyte receptors due to its stability, fine secretability and strong preS1 antigenicity.
通过聚合酶链反应(PCR)构建了四对前S区部分缺失的乙肝病毒表面抗原基因。对这些基因与之前构建的基因在哺乳动物细胞中的表达水平以及这些基因产物的特性进行比较后发现,前S区部分缺失并不影响S区的整体空间结构以及前S区的表面定位。去除前S1保留序列(氨基酸2 - 19)可显著减轻前S序列对S区主要抗原决定簇的遮蔽作用。研究发现,长前S区严重损害哺乳动物细胞表面抗原蛋白的分泌。除了先前报道的前S1保留序列外,前S1序列(氨基酸48 - 65)也可能抑制表面抗原蛋白的分泌,而前S2区对大表面抗原蛋白的保留没有重大影响。其中一种表达的表面抗原蛋白,其前S1序列(氨基酸21 - 47)与S区直接融合,因其稳定性、良好的分泌性和强前S1抗原性,值得进一步研究,可能开发成为一种含有肝细胞受体前S1结合位点的新型乙肝疫苗。