Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
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DOI：
10.1128/mbio.02764-19
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发表时间：
2020-01-01
期刊：
影响因子：
6.4
通讯作者：
Gallagher, Tom
中科院分区：
文献类型：
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作者：
Qing, Enya;Hantak, Michael;Gallagher, Tom
冠状病毒(CoV)是人类和动物常见的病原体，可通过人畜传播并导致严重的呼吸道疾病综合征。冠状病毒感染需要刺突蛋白，它将病毒结合到宿主细胞受体上，并催化病毒-细胞膜融合。几个冠状病毒毒株都有带有两个受体结合域的刺突蛋白，一个是与宿主唾液酸结合的S1a，另一个是识别宿主跨膜蛋白的S1b。由于这种双价结合可能使人畜共患冠状病毒广泛感染，我们的目的是确定每个受体在不同感染阶段的作用。针对两种β冠状病毒，小鼠JHM冠状病毒和人中东呼吸综合征冠状病毒(MERS-CoV)，我们发现病毒颗粒与细胞的结合是由唾液酸介导的；然而，随后的病毒感染需要跨膜蛋白受体。这些结果支持一个两步过程，在这个过程中，病毒首先附着在唾液酸上，然后在感染细胞进入时需要随后与蛋白质受体接触。然而，唾液酸充分促进了病毒通过细胞-细胞膜融合传播的后期阶段，而不需要蛋白质受体。在缺乏原型蛋白受体的情况下，这种病毒的传播通过适应性S1a突变而增加。总体而言，这些发现揭示了唾液酸在病毒与细胞结合、病毒刺突蛋白引导的细胞-细胞融合以及由此导致的冠状病毒感染传播中的作用。这种人畜共患病传播使用尖峰蛋白，它将冠状病毒与具有两个受体结合结构域的细胞结合。在这里，我们确定了两个结合过程在冠状病毒感染过程中的作用。与唾液酸的结合促进了感染，并通过合胞发育支持冠状病毒感染的细胞间扩张。唾液酸结合刺激区的适应性突变增加了细胞间的扩张过程。这些发现提出了这样一种可能性，即许多冠状病毒的凝集素样特性有助于在受感染的有机体内容易地进行人畜共患传播和细胞间传播。
Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.