Association of hepatitis C virus envelope proteins with exosomes
Association of hepatitis C virus envelope proteins with exosomes
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DOI：
10.1002/eji.200424887
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Abrignani, S
中科院分区：
文献类型：
--
作者：
Masciopinto, F;Giovani, C;Abrignani, S
由于人四跨膜蛋白CD 81与丙型肝炎病毒（HCV）包膜糖蛋白E2结合，我们探讨了CD 81在HCV包膜蛋白细胞运输中可能发挥的作用。由于缺乏稳定的细胞培养系统，对HCV生命周期的研究变得复杂;因此，我们用HCV E1-E2 cDNA转染哺乳动物细胞，有或没有人CD 81（huCD 81）cDNA。在不存在huCD 81的情况下，HCV包膜蛋白几乎完全保留在内质网中。相反，当huCD 81存在时，一部分HCV包膜蛋白穿过高尔基体，成熟获得复合糖，并发现与外泌体细胞外相关。这些是富含四跨膜蛋白的60-100 nm膜囊泡，由许多细胞类型释放到细胞外环境中，并具有融合活性。我们还报告说，人血浆中含有外泌体，在HCV患者中，病毒RNA与这些循环囊泡相关。我们提出HCV-CD 81复合物以外泌体的形式离开细胞，以这种形式循环，并利用这些囊泡的融合能力来感染细胞，即使在中和抗体存在的情况下也是如此。
As the human tetraspanin CD81 binds hepatitis C virus (HCV) envelope glycoprotein E2, we addressed the role CD81 may play in cellular trafficking of HCV envelope proteins. Studies on HCV life cycle are complicated by the lack of a robust cell culture system; we therefore transfected mammalian cells with HCV E1-E2 cDNA, with or without human CD81 (huCD81) cDNA. In the absence of huCD81, HCV envelope proteins are almost completely retained in the endoplasmic reticulum. Instead, when huCD81 is present, a fraction of HCV envelope proteins passes through the Golgi apparatus, matures acquiring complex sugars and is found extracellularly associated with exosomes. These are 60-100-nm membrane vesicles enriched in tetraspanins, released into the extracellular milieu by many cell types and having fusogenic activity. We also report that human plasma contains exosomes and that in HCV patients, viral RNA is associated with these circulating vesicles. We propose that the HCV-CD81 complex leaves cells in the form of exosomes, circulates in this form and exploits the fusogenic capabilities of these vesicles to infect cells even in the presence of neutralizing antibodies.