Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells.
Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells.
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DOI：
10.1074/jbc.ra118.001897
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发表时间：
2018-07-27
期刊：
影响因子：
--
通讯作者：
Yuen KY
中科院分区：
文献类型：
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作者：
Chu H;Chan CM;Zhang X;Wang Y;Yuan S;Zhou J;Au-Yeung RK;Sze KH;Yang D;Shuai H;Hou Y;Li C;Zhao X;Poon VK;Leung SP;Yeung ML;Yan J;Lu G;Jin DY;Gao GF;Chan JF;Yuen KY
冠状病毒的嗜性主要由冠状病毒刺突与宿主受体的相互作用决定。在这方面，冠状病毒通过其刺突蛋白进化出了复杂的受体识别系统。来自高度相关的冠状病毒的刺突可以识别不同的受体，而来自远距离的冠状病毒的刺突可以利用相同的细胞表面分子进入。此外，冠状病毒刺突除了识别受体外，还能识别广泛的细胞表面分子，从而增强冠状病毒的附着或进入。中东呼吸综合征冠状病毒（MERS-CoV）受体是二肽基肽酶4 （DPP4）。在这项研究中，我们确定了膜相关的78 kda葡萄糖调节蛋白（GRP78）作为MERS-CoV刺突的另一个结合靶标。进一步分析表明，GRP78不能单独使非受纳细胞对MERS-CoV感染易感，但可以通过增加病毒附着来促进MERS-CoV进入受纳细胞。更重要的是，通过探索GRP78与其他冠状病毒刺突之间的潜在相互作用，我们发现高度保守的人类GRP78可以与蝙蝠冠状病毒HKU9 （bCoV-HKU9）刺突蛋白相互作用，并促进其附着在宿主细胞表面。综上所述，我们的研究已经确定GRP78是一种宿主因子，可以与两种β冠状病毒（C系MERS-CoV和D系bCoV-HKU9）的刺突蛋白相互作用。GRP78能够促进人类冠状病毒和与系统发育相关的蝙蝠冠状病毒的表面附着，这表明需要持续监测动物冠状病毒的进化，以监测其适应人类的潜力。
Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.