pH-dependent entry of Severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN
pH-dependent entry of Severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN
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DOI：
10.1128/jvi.78.11.5642-5650.2004
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Yang, ZY;Huang, Y;Nabel, GJ
严重急性呼吸综合征冠状病毒（SARS-CoV）合成了几种推定的病毒包膜蛋白，包括刺突（S）、膜（M）和小包膜（E）糖蛋白。虽然这些蛋白质可能是病毒复制所必需的，但它们在SARS-CoV进入中的具体作用尚未确定。在这份报告中，我们表明SARS-CoV S糖蛋白通过pH依赖性内吞作用介导病毒进入。此外，我们定义了它的细胞向性，并证明病毒传播发生通过树突状细胞介导的转移。S糖蛋白被成功地用于假型复制缺陷型逆转录病毒和慢病毒载体，容易感染Vero细胞，以及初级肺和肾上皮细胞从人类，非人灵长类动物，并在较小程度上，猫科动物物种。该报告病毒的嗜性类似于野生型，复制能力的SARS-CoV，并通过流式细胞术证明了纯化的S敏感的靶细胞的结合。虽然骨髓树突状细胞能够与S相互作用并结合病毒，但这些细胞不能被SARS-CoV感染。然而，这些细胞能够通过突触样结构将病毒转移到易感的靶细胞。细胞介导的感染和直接感染的抑制抗S抗血清，这表明针对这种基因产物的策略可能会赋予抗病毒药物或SARS疫苗的发展的治疗效益。
The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis. Further, we define its cellular tropism and demonstrate that virus transmission occurs through cell-mediated transfer by dendritic cells. The S glycoprotein was used successfully to pseudotype replication-defective retroviral and lentiviral vectors that readily infected Vero cells as well as primary pulmonary and renal epithelial cells from human, nonhuman primate, and, to a lesser extent, feline species. The tropism of this reporter virus was similar to that of wild-type, replication-competent SARS-CoV, and binding of purified S to susceptible target cells was demonstrated by flow cytometry. Although myeloid dendritic cells were able to interact with S and to bind virus, these cells could not be infected by SARS-CoV. However, these cells were able to transfer the virus to susceptible target cells through a synapse-like structure. Both cell-mediated infection and direct infection were inhibited by anti-S antisera, indicating that strategies directed toward this gene product are likely to confer a therapeutic benefit for antiviral drugs or the development of a SARS vaccine.