Tan Yongjun, Schneider Theresa, Leong Matthew, Aravind L, Zhang Dapeng
Department of Biology, College of Arts and Sciences, Saint Louis University, MO 63110.
School of Medicine, Saint Louis University, MO 63110.
bioRxiv. 2020 Mar 7:2020.03.04.977736. doi: 10.1101/2020.03.04.977736.
A novel coronavirus (SARS-CoV-2) is the causative agent of an emergent severe respiratory disease (COVID-19) in humans that is threatening to result in a global health crisis. By using genomic, sequence, structural and evolutionary analysis, we show that Alpha- and Beta-CoVs possess several novel families of immunoglobulin (Ig) domain proteins, including ORF8 and ORF7a from SARS-related coronaviruses and two protein groups from certain Alpha-CoVs. Among them, ORF8 is distinguished in being rapidly evolving, possessing a unique insert and a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover many Ig proteins from several metazoan viruses which are distinct in sequence and structure but share an architecture comparable to that of CoV Ig domain proteins. Hence, we propose that deployment of Ig domain proteins is a widely-used strategy by viruses, and SARS-CoV-2 ORF8 is a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts.
一种新型冠状病毒（SARS-CoV-2）是人类一种新出现的严重呼吸道疾病（COVID-19）的病原体，该疾病有可能导致全球健康危机。通过基因组、序列、结构和进化分析，我们发现α冠状病毒和β冠状病毒拥有几个新的免疫球蛋白（Ig）结构域蛋白家族，包括来自与SARS相关冠状病毒的ORF8和ORF7a以及某些α冠状病毒的两个蛋白组。其中，ORF8的特点是进化迅速，在其预测的配体结合槽中，在SARS-CoV-2基因组中具有独特的插入序列和一个高变位点。我们还从几种后生动物病毒中发现了许多Ig蛋白，它们在序列和结构上各不相同，但具有与冠状病毒Ig结构域蛋白相当的结构。因此，我们提出，Ig结构域蛋白的部署是病毒广泛使用的一种策略，而SARS-CoV-2的ORF8是一种潜在的致病因素，它迅速进化以对抗免疫反应并促进宿主间的传播。
