Zhang Jie, Randall Glenn, Higginbottom Adrian, Monk Peter, Rice Charles M, McKeating Jane A
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, New York 10021, USA.
J Virol. 2004 Feb;78(3):1448-55. doi: 10.1128/jvi.78.3.1448-1455.2004.
CD81 has been described as a putative receptor for hepatitis C virus (HCV); however, its role in HCV cell entry has not been characterized due to the lack of an efficient cell culture system. We have examined the role of CD81 in HCV glycoprotein-dependent entry by using a recently developed retroviral pseudotyping system. Human immunodeficiency virus (HIV) pseudotypes bearing HCV E1E2 glycoproteins show a restricted tropism for human liver cell lines. Although all of the permissive cell lines express CD81, CD81 expression alone is not sufficient to allow viral entry. CD81 is required for HIV-HCV pseudotype infection since (i) a monoclonal antibody specific for CD81 inhibited infection of susceptible target cells and (ii) silencing of CD81 expression in Huh-7.5 hepatoma cells by small interfering RNAs inhibited HIV-HCV pseudotype infection. Furthermore, expression of CD81 in human liver cells that were previously resistant to infection, HepG2 and HH29, conferred permissivity of HCV pseudotype infection. The characterization of chimeric CD9/CD81 molecules confirmed that the large extracellular loop of CD81 is a determinant for viral entry. These data suggest a functional role for CD81 as a coreceptor for HCV glycoprotein-dependent viral cell entry.
CD81被认为是丙型肝炎病毒(HCV)的假定受体;然而,由于缺乏有效的细胞培养系统,其在HCV细胞进入过程中的作用尚未得到明确。我们通过使用最近开发的逆转录病毒假型系统,研究了CD81在HCV糖蛋白依赖性进入过程中的作用。携带HCV E1E2糖蛋白的人类免疫缺陷病毒(HIV)假型对人肝细胞系表现出有限的嗜性。尽管所有允许感染的细胞系都表达CD81,但仅CD81的表达不足以允许病毒进入。CD81是HIV-HCV假型感染所必需的,因为(i)一种针对CD81的单克隆抗体抑制了易感靶细胞的感染,并且(ii)小干扰RNA使Huh-7.5肝癌细胞中的CD81表达沉默,从而抑制了HIV-HCV假型感染。此外,在先前对感染具有抗性的人肝细胞HepG2和HH29中表达CD81,赋予了HCV假型感染的易感性。嵌合CD9/CD81分子的特性证实,CD81的大细胞外环是病毒进入的决定因素。这些数据表明CD81作为HCV糖蛋白依赖性病毒细胞进入的共受体具有功能性作用。