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前S区有缺失的乙肝病毒表面抗原蛋白

HBV surface antigen proteins with deletions in the preS region.

作者信息

Xu K, Yu X, Kong Y, Wang Y, Li Z

机构信息

Shanghai Institute of Biochemistry, Chinese Academy of Sciences.

出版信息

Sci China B. 1995 Mar;38(3):320-7.

PMID:7766314
Abstract

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.

摘要

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。

相似文献

1
HBV surface antigen proteins with deletions in the preS region.前S区有缺失的乙肝病毒表面抗原蛋白
Sci China B. 1995 Mar;38(3):320-7.
2
[Study on HBV preS/S gene mutation in peripheral blood mononuclear cells].
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 1999 Jun 30;13(2):148-52.
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A C-terminal PreS1 sequence is sufficient to retain hepatitis B virus L protein in 293 cells.C末端前S1序列足以将乙型肝炎病毒L蛋白保留在293细胞中。
Virology. 1995 Oct 20;213(1):57-69. doi: 10.1006/viro.1995.1546.
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An HBV large surface antigen protein which can be secreted from mammalian cells.一种可从哺乳动物细胞分泌的乙肝病毒大表面抗原蛋白。
Sci China B. 1992 Apr;35(4):455-62.
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[Enhancing immunogenicity of pres antigen of hepatitis B virus by fusing genetically it with interleukin-2].[通过将乙肝病毒前S抗原与白细胞介素-2基因融合增强其免疫原性]
Zhonghua Yi Xue Za Zhi. 1996 Jan;76(1):34-7.
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Naturally occurring woodchuck hepatitis virus (WHV) deletion mutants in chronically WHV-infected woodchucks.慢性感染土拨鼠肝炎病毒(WHV)的土拨鼠体内自然产生的WHV缺失突变体。
Virology. 2000 Nov 25;277(2):226-34. doi: 10.1006/viro.1999.0127.
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[Simultaneous expression of modified hepatitis B surface antigen fusion polypeptides containing preS1, preS2 epitopes in Pichia pastoris].[含前S1、前S2表位的修饰乙肝表面抗原融合多肽在毕赤酵母中的同时表达]
Sheng Wu Gong Cheng Xue Bao. 2006 Jul;22(4):604-8.
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Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease.乙型肝炎病毒基因型对前S区缺失及晚期肝病发生发展的影响。
J Med Virol. 2003 Aug;70(4):537-44. doi: 10.1002/jmv.10428.
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The prevalence of hepatitis B virus preS deletions occurring naturally in Korean patients infected chronically with genotype C.在慢性感染C基因型的韩国患者中自然发生的乙肝病毒前S区缺失的流行情况。
J Med Virol. 2008 Jul;80(7):1189-94. doi: 10.1002/jmv.21208.
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Expression and secretion of preS containing hepatitis B surface antigen in vaccinia virus system.
Sci China B. 1990 Sep;33(9):1070-7.

引用本文的文献

1
A Multivalent mRNA Therapeutic Vaccine Exhibits Breakthroughs in Immune Tolerance and Virological Suppression of HBV by Stably Presenting the Pre-S Antigen on the Cell Membrane.一种多价mRNA治疗性疫苗通过在细胞膜上稳定呈现前S抗原,在乙肝病毒的免疫耐受和病毒学抑制方面取得突破。
Pharmaceutics. 2025 Feb 7;17(2):211. doi: 10.3390/pharmaceutics17020211.