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对缺乏丝氨酸蛋白酶抑制剂基因的重组痘苗病毒表达的人乳头瘤病毒16型L1蛋白的抗体反应增强。

Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes.

作者信息

Zhou J, Crawford L, McLean L, Sun X Y, Stanley M, Almond N, Smith G L

机构信息

Department of Pathology, University of Cambridge, U.K.

出版信息

J Gen Virol. 1990 Sep;71 ( Pt 9):2185-90. doi: 10.1099/0022-1317-71-9-2185.

DOI:10.1099/0022-1317-71-9-2185
PMID:2170578
Abstract

The L1 gene of human papillomavirus type 16 (HPV-16) driven by the vaccinia virus major late 4b gene promoter has been inserted into three different sites of the vaccinia virus genome. Insertion into the thymidine kinase (TK) gene was achieved by selection of TK- mutants in BUdR on TK- cells. Insertion into two vaccinia virus serine protease inhibitor (serpin) genes was achieved by co-insertion of the Escherichia coli xanthine guanine phosphoribosyltransferase gene linked to the vaccinia virus 7.5K promoter and selection of mycophenolic acid-resistant recombinant viruses. Each recombinant virus expressed a 57K L1 protein at similar levels and with similar kinetics. However, immunization of mice with these recombinant viruses induced different levels of antibody to the L1 protein. Viruses lacking serpin genes B13R and B24R induced significantly higher antibody levels than did viruses lacking the TK gene. The presence of functional B13R and B24R gene products is therefore somehow immunosuppressive at least for antibody responses to the L1 protein of HPV-16.

摘要

由痘苗病毒主要晚期4b基因启动子驱动的人乳头瘤病毒16型(HPV - 16)L1基因已被插入痘苗病毒基因组的三个不同位点。通过在TK⁻细胞上在溴脱氧尿苷(BUdR)中选择TK⁻突变体,实现了将其插入胸苷激酶(TK)基因。通过共插入与痘苗病毒7.5K启动子相连的大肠杆菌黄嘌呤鸟嘌呤磷酸核糖转移酶基因并选择对霉酚酸耐药的重组病毒,实现了将其插入两个痘苗病毒丝氨酸蛋白酶抑制剂(serpin)基因。每种重组病毒都以相似的水平和相似的动力学表达一种57K的L1蛋白。然而,用这些重组病毒免疫小鼠诱导出不同水平的针对L1蛋白的抗体。缺乏serpin基因B13R和B24R的病毒诱导的抗体水平明显高于缺乏TK基因的病毒。因此,功能性B13R和B24R基因产物的存在至少在某种程度上对HPV - 16 L1蛋白的抗体反应具有免疫抑制作用。

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