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Viruses are acellular organisms that must be parasitized in living cells and proliferated by replication. Although different viruses invade cells in different ways, they mainly initiate the invasion process through binding to specific receptor proteins or lipid structures on the cell surface for the following cellular internalization. Thus revealing the interaction process and underlying mechanism between viruses and cell membranes will be helpful in developing targeted drugs or vaccines from the source. In this review, the influenza virus and coronavirus are taken for example. We will first discuss the structure of influenza viruses, their binding modes with cell membranes, the way of realizing cell endocytosis and the cytokines involved in this process. After that, recent research progress of coronavirus especially the novel coronavirus SARS-CoV-2, including its structural characteristics, its binding with cell receptor ACE2 and the following cellular internalization, is briefly introduced.
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Keywords:
- influenza virus /
- novel coronavirus SARS-CoV-2 /
- cellular internalization /
- clathrin-mediated endocytosis
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图 1 流感病毒的结构与形状[17,21] (a) 丝状、杆状与球状流感病毒模型图, 流感病毒是包被病毒, 最外层是脂质膜, 膜上含有HA和NA两种糖蛋白及M2通道蛋白, 膜下是基质蛋白M1, 丝状病毒的基因组位于远端, 球状病毒的基因组位于中心; (b) 丝状病毒和(c) 球状病毒的电子显微镜照片
Figure 1. Composition and shape of influenza virus[17,21]: (a) Filamentous, rod-shaped and globular influenza virus models; (b), (c) representative electron microscopy images of filamentous and globular viruses, respectively.
图 2 流感病毒在细胞表面结合及内化示意图. 流感病毒与细胞表面的糖蛋白或糖脂末端的唾液酸、或者磷酸化的糖蛋白、抑或是C型凝集素Langerin发生结合, 之后在G蛋白偶联受体FFAR2、表达于膜上的核仁蛋白、适配体蛋白Epsin1和EPS15、C型凝集素Langerin等细胞因子的参与下, 通过网格蛋白介导的方式发生内吞. 胞内Ca2+的增加可以促进流感病毒通过网格蛋白或非网格蛋白的方式侵入细胞, 另外膜上脂筏结构也参与病毒的吸附和内化过程
Figure 2. Schematic diagram of influenza virus binding and internalization at cellular surface. The influenza virus binds on the cell surface with sialic acid at the end of a glycoprotein or lipid, phosphorylated glycoprotein, or C-type lectin Langerin, and then enters into the cell through clathrin-mediated endocytosis with the participation of cytokines such as G protein coupled receptor FFAR2, nucleolus protein expressed in membrane, adapter proteins Epsin1 and EPS15, or C-type lectin Langerin. An increased amount of intracellular Ca2+ promotes the entry of influenza virus in the clathrin or non-clathrin way. Lipid rafts also play roles in the process of virus adsorption and internalization.
表 1 流感病毒与宿主细胞结合的靶向分子
Table 1. Targeting molecules for influenza virus binding to host cells.
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