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Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species.
Journal of Virology ( IF 4.0 ) Pub Date : 2020-02-14 , DOI: 10.1128/jvi.01387-19
Yuan Yuan 1 , Jianxun Qi 1 , Ruchao Peng 1 , Chunrui Li 1 , Guangwen Lu 2 , Jinghua Yan 1, 3, 4 , Qihui Wang 4, 5 , George Fu Gao 4, 6, 7, 8
Affiliation  

Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.

中文翻译:

中东呼吸综合征冠状病毒与来自七个蝙蝠物种的CD26结合的分子基础。

自2012年鉴定出中东呼吸综合征冠状病毒(MERS-CoV)以来,一直有感染人类的​​报道。中东呼吸综合征冠状病毒(MERS-CoV)容易在中东地区引起地方性疾病,数十起溢出感染向其他大洲蔓延。据推测,MERS-CoV源于蝙蝠冠状病毒,而单峰骆驼是其天然库。尽管从某些种类的蝙蝠中测序出与MERS-CoV相同的基因片段,并且其中一个物种通过实验释放了该病毒,但仍不清楚其他蝙蝠是否可以传播该病毒。在分子水平上,我们发现来自各种物种的所有纯化蝙蝠CD26(bCD26)与MERS-CoV的受体结合域(RBD)相互作用,平衡解离常数值在微摩尔水平范围从几到数百不等。此外,在这项研究中表达的所有bCD26s介导假型MERS-CoV进入受体表达细胞,表明bCD26s作为MERS-CoV受体具有广泛的潜在参与性。进一步的结构分析表明,与人类受体相比,蝙蝠受体中关键残基及其邻近氨基酸的取代导致与MERS-RBD的结合亲和力降低。这些结果为现有的观点提供了更多证据,即蝙蝠是MERS-CoV的原始来源,并表明许多物种中的bCD26s可以介导病毒的进入,这对于MERS-CoV感染的监视和控制具有重要意义。在这个研究中,我们发现不同物种的蝙蝠CD26s(bCD26s)表现出很大的多样性,尤其是在负责与中东呼吸综合征冠状病毒(MERS-CoV)的受体结合域(RBD)结合的区域。但是,它们以不同的亲和力保持与MERS-RBD的相互作用,并支持假型MERS-CoV的进入。这些蝙蝠受体多态性似乎赋予适应CD26结合病毒(如MERS-CoV的祖先)的进化压力,并导致产生了多种与CD26结合的CoV菌株。因此,我们的数据增加了更多的证据来支持蝙蝠是MERS-CoV和类似病毒的库,并且进一步强调了调查蝙蝠中MERS-CoV和其他CoV的必要性。特别是在负责与中东呼吸综合征冠状病毒(MERS-CoV)的受体结合域(RBD)结合的区域。但是,它们以不同的亲和力保持与MERS-RBD的相互作用,并支持假型MERS-CoV的进入。这些蝙蝠受体多态性似乎赋予适应CD26结合病毒(如MERS-CoV的祖先)的进化压力,并导致产生了多种与CD26结合的CoV菌株。因此,我们的数据提供了更多证据来证明蝙蝠是MERS-CoV和类似病毒的储存库,并且进一步强调了调查蝙蝠中MERS-CoV和其他CoV的必要性。特别是在负责与中东呼吸综合征冠状病毒(MERS-CoV)的受体结合域(RBD)结合的区域。但是,它们以不同的亲和力保持与MERS-RBD的相互作用,并支持假型MERS-CoV的进入。这些蝙蝠受体多态性似乎赋予适应CD26结合病毒(如MERS-CoV的祖先)的进化压力,并导致产生了多种与CD26结合的CoV菌株。因此,我们的数据增加了更多的证据来支持蝙蝠是MERS-CoV和类似病毒的库,并且进一步强调了调查蝙蝠中MERS-CoV和其他CoV的必要性。它们以不同的亲和力保持与MERS-RBD的相互作用,并支持假型MERS-CoV的进入。这些蝙蝠受体多态性似乎赋予适应CD26结合病毒(如MERS-CoV的祖先)的进化压力,并导致产生了多种与CD26结合的CoV菌株。因此,我们的数据增加了更多的证据来支持蝙蝠是MERS-CoV和类似病毒的库,并且进一步强调了调查蝙蝠中MERS-CoV和其他CoV的必要性。它们以不同的亲和力保持与MERS-RBD的相互作用,并支持假型MERS-CoV的进入。这些蝙蝠受体多态性似乎赋予适应CD26结合病毒(如MERS-CoV的祖先)的进化压力,并导致产生了多种与CD26结合的CoV菌株。因此,我们的数据提供了更多证据来证明蝙蝠是MERS-CoV和类似病毒的储存库,并且进一步强调了调查蝙蝠中MERS-CoV和其他CoV的必要性。
更新日期:2019-11-01
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