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宿主免疫反应推动新冠病毒进化。

Host immune response driving SARS-CoV-2 evolution.

作者信息

Wang Rui, Hozumi Yuta, Zheng Yong-Hui, Yin Changchuan, Wei Guo-Wei

出版信息

ArXiv. 2020 Aug 20:arXiv:2008.07488v2.

Abstract

The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance to the controlling and combating of coronavirus disease 2019 (COVID-19) pandemic. Currently, near 15,000 SARS-CoV-2 single mutations have been recorded, having a great ramification to the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2 evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response via APOBEC and ADAR gene editing gives rise to near 65% of recorded mutations. Additionally, we show that children under age five and the elderly may be at high risk from COVID-19 because of their overreacting to the viral infection. Moreover, we uncover that populations of Oceania and Africa react significantly more intensively to SARS-CoV-2 infection than those of Europe and Asia, which may explain why African Americans were shown to be at increased risk of dying from COVID-19, in addition to their high risk of getting sick from COVID-19 caused by systemic health and social inequities. Finally, our study indicates that for two viral genome sequences of the same origin, their evolution order may be determined from the ratio of mutation type C$>$T over T$>$C.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的传播与进化对于控制和抗击2019冠状病毒病(COVID-19)大流行至关重要。目前,已记录了近15000个SARS-CoV-2单突变,这对诊断、疫苗、抗体疗法及药物的研发产生了重大影响。然而,人们对SARS-CoV-2的进化特征和总体趋势知之甚少。在这项研究中,我们对现有的SARS-CoV-2突变进行了全面的基因分型分析。我们发现,通过载脂蛋白B mRNA编辑酶催化多肽样蛋白(APOBEC)和腺苷脱氨酶作用于RNA(ADAR)基因编辑产生的宿主免疫反应导致了近65%的已记录突变。此外,我们表明,五岁以下儿童和老年人可能因对病毒感染反应过度而面临较高的COVID-19风险。而且,我们发现大洋洲和非洲人群对SARS-CoV-2感染的反应比欧洲和亚洲人群更为强烈,这或许可以解释为什么非裔美国人除了因系统性健康和社会不平等导致感染COVID-19的风险较高外,死于COVID-19的风险也有所增加。最后,我们的研究表明,对于两个同源的病毒基因组序列,其进化顺序可由C>T突变类型与T>C突变类型的比例来确定。

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