Abstract：
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high mutation rate and many variants have emerged in the last 2 years, including Alpha, Beta, Delta, Gamma and Omicron. Studies showed that the host-genome similarity (HGS) of SARS-CoV-2 is higher than SARS-CoV and the HGS of open reading frame (ORF) in coronavirus genome is closely related to suppression of innate immunity. Many works have shown that ORF 6 and ORF 8 of SARS-CoV-2 play an important role in suppressing IFN-β signaling pathway in vivo. However, the relation between HGS and the adaption of SARS-CoV-2 variants is still not clear. This work investigates HGS of SARS-CoV-2 variants based on a dataset containing more than 40,000 viral genomes. The relation between HGS of viral ORFs and the suppression of antivirus response is studied. The results show that ORF 7b, ORF 6 and ORF 8 are the top 3 genes with the highest HGS. In the past 2 years, the HGS values of ORF 8 and ORF 7B of SARS-CoV-2 have increased greatly. A remarkable correlation is discovered between HGS and inhibition of antivirus response of immune system, which suggests that the similarity between coronavirus and host gnome may be an indicator of the suppression of innate immunity. Among the five variants (Alpha, Beta, Delta, Gamma and Omicron), Delta has the highest HGS and Omicron has the lowest HGS. This finding implies that the high HGS in Delta variant may indicate further suppression of host innate immunity. However, the relatively low HGS of Omicron is still a puzzle. By comparing the mutations in genomes of Alpha, Delta and Omicron variants, a commonly shared mutation ACT > ATT is identified in high-HGS strain populations. The high HGS mutations among the three variants are quite different. This finding strongly suggests that mutations in high HGS strains are different in different variants. Only a few common mutations survive, which may play important role in improving the adaptability of SARS-CoV-2. However, the mechanism for how the mutations help SARS-CoV-2 escape immunity is still unclear. HGS analysis is a new method to study virus−host interaction and may provide a way to understand the rapid mutation and adaption of SARS-CoV-2.
摘要：
严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）具有很高的突变率，并且在过去2年中出现了许多变体，包括阿尔法,Beta,Delta,Gamma和Omicron.研究表明，SARS-CoV-2的宿主基因组相似性（HGS）高于SARS-CoV，冠状病毒基因组中开放阅读框（ORF）的HGS与先天免疫的抑制密切相关。许多工作表明SARS-CoV-2的ORF6和ORF8在体内抑制IFN-β信号通路中起重要作用。然而,HGS与SARS-CoV-2变种的适应性之间的关系尚不清楚。这项工作基于包含40,000多个病毒基因组的数据集调查了SARS-CoV-2变体的HGS。研究了病毒ORF的HGS与抗病毒反应抑制之间的关系。结果表明，ORF7b，ORF6和ORF8是HGS最高的前3个基因。在过去的两年里,SARS-CoV-2的ORF8和ORF7B的HGS值大大增加。发现HGS与抑制免疫系统的抗病毒反应之间存在显着相关性，这表明冠状病毒和宿主侏儒之间的相似性可能是先天免疫抑制的指标。在五个变体中(Alpha，Beta,Delta,Gamma和Omicron)，Delta的HGS最高，Omicron的HGS最低。该发现暗示Delta变体中的高HGS可能指示宿主先天免疫的进一步抑制。然而,Omicron的相对较低的HGS仍然是一个难题。通过比较Alpha基因组的突变,Delta和Omicron变体，在高HGS菌株群体中鉴定出通常共有的突变ACT>ATT。三种变体中的高HGS突变是相当不同的。该发现强烈表明高HGS菌株中的突变在不同变体中是不同的。只有少数常见突变存活下来,这可能对提高SARS-CoV-2的适应性具有重要作用。然而,这些突变如何帮助SARS-CoV-2逃避免疫的机制尚不清楚.HGS分析是研究病毒-宿主相互作用的一种新方法，可能为了解SARS-CoV-2的快速突变和适应提供一种方法。
