Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates
Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates
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DOI：
10.1016/j.heliyon.2020.e04818
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发表时间：
2020-09-01
期刊：
影响因子：
4
通讯作者：
Sang, Yongming
中科院分区：
文献类型：
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作者：
Sang, Eric R.;Tian, Yun;Sang, Yongming
目前的新型冠状病毒病(新冠肺炎)已在全球200多个国家和地区造成400/600多万确诊死亡/感染病例。作为病原性冠状病毒(又名SARS冠状病毒(SARS-CoV2)可能起源于蝙蝠，但我们对其在蝙蝠和人类之间的中间储存库，特别是在野生和家养动物中的嗜性的了解大多未知。这对当前的流行病和潜在的人畜共患病构成了公共卫生方面的重大关切。以前的报道使用与其细胞受体血管紧张素转换酶2(ACE2)结合的病毒尖峰蛋白(S)的结构分析表明，在野生动物，特别是家畜中，SARS-CoV2的易感性具有广泛的潜力。通过整合关键的免疫遗传因素，包括S结合无效血管紧张素转换酶2亚型的存在和血管紧张素转换酶2在早期先天免疫反应中表达的差异，我们进一步完善了SARS-CoV2易感性的预测，以符合最近的实验验证。除了基于结构分析在哺乳动物物种中显示出广泛的易感潜力外，我们的结果还显示，包括狗、猪、牛和山羊在内的家畜可能进化出与ACE2相关的免疫遗传多样性，以限制SARS-CoV2的感染。因此，我们认为，家养动物可能不太可能扮演放大宿主的角色，除非病毒有进一步的物种特异性适应。这些发现可能会缓解公众对家畜中类似新冠肺炎风险的担忧，突出病毒与宿主的共同进化，并通过靶向血管紧张素转换酶2分子多样性和干扰素优化引发疾病干预。
The current new coronavirus disease (COVID-19) has caused globally over 0.4/6 million confirmed deaths/ infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. Findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization.