Sang Eric R, Tian Yun, Gong Yuanying, Miller Laura C, Sang Yongming
Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USA.
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.
Heliyon. 2020 Sep;6(9):e04818. doi: 10.1016/j.heliyon.2020.e04818. Epub 2020 Aug 31.
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.
当前的新型冠状病毒病（COVID-19）已在全球200多个国家造成超过40万例确诊死亡/感染病例。由于病原性冠状病毒（即SARS-CoV2）可能推测起源于蝙蝠，我们对其在蝙蝠和人类之间的中间宿主，尤其是其在野生动物和家畜中的嗜性了解甚少。这构成了当前大流行和潜在人畜共患病在公共卫生方面的主要担忧。先前使用病毒刺突蛋白（S）与其细胞受体血管紧张素转换酶2（ACE2）结合的结构分析报告表明，SARS-CoV2在野生动物尤其是家畜中具有广泛的易感性。通过整合关键免疫遗传因素，包括存在与S结合无效的ACE2异构体以及早期先天免疫反应时ACE2表达的差异，我们进一步完善了SARS-CoV2易感性预测，以符合最近的实验验证。除了基于结构分析显示出跨哺乳动物物种的广泛易感性潜力外，我们的结果还表明，包括狗、猪、牛和山羊在内的家畜可能会进化出与ACE2相关的免疫遗传多样性以限制SARS-CoV2感染。因此，我们提出，除非病毒有进一步的物种特异性适应，家畜不太可能起到扩增宿主的作用。这些发现可能会缓解公众对家畜中类似COVID-19风险的相关担忧，突出病毒-宿主共同进化，并通过靶向ACE2分子多样性和优化干扰素来引发疾病干预。
