Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus
Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus
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DOI：
10.1002/j.1460-2075.1996.tb00803.x
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发表时间：
1996-08-15
期刊：
影响因子：
11.4
通讯作者：
Feinstone, SM
中科院分区：
文献类型：
--
作者：
Kaplan, G;Totsuka, A;Feinstone, SM
关于甲型肝炎病毒（HAV）进入细胞的机制知之甚少，并且这种小核糖核酸病毒的细胞受体的鉴定一直是难以捉摸的。本研究利用针对易感非洲绿猴肾（AGMK）细胞的保护性单克隆抗体作为探针，克隆了一种HAV细胞受体。单克隆抗体190/4、235/4和263/6针对相似的表位反应，通过阻断HAV的结合，特异性地保护AGMK细胞免受HAV感染。对表位190/4的cDNA编码进行克隆和核苷酸序列分析，发现了一个含有451个氨基酸的新型粘蛋白样I类完整膜糖蛋白，即HAV细胞受体1 （HAV cr-1）。免疫荧光肛门;研究表明，转染HAV cr-1 cDNA的小鼠Ltk（-）细胞对HAV感染具有有限的易感性，单克隆抗体190/4可阻断这种易感性。我们的研究结果表明，HAV cr-1多肽是HAV的附着受体，强烈提示它也是介导HAV感染的功能性受体，这是首次鉴定出HAV的细胞受体。
Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes, Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV, Expression; cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAV cr-1). Immunofluorescence anal;sis indicated that mouse Ltk(-) cells transfected with HAV cr-1 cDNA gained Limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4, Our results demonstrate that the HAV cr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection, This report constitutes the first identification of a cellular receptor for HAV.