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宿主免疫反应驱动 SARS-CoV-2 进化。

Host Immune Response Driving SARS-CoV-2 Evolution.

机构信息

Department of Mathematics, Michigan State University, East Lansing, MI 48824, USA.

Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.

出版信息

Viruses. 2020 Sep 27;12(10):1095. doi: 10.3390/v12101095.

Abstract

The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in controlling and combating the coronavirus disease 2019 (COVID-19) pandemic. Currently, over 15,000 SARS-CoV-2 single mutations have been recorded, which have a great impact on the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2's 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 overreaction 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 COVID-19 infection 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) 的传播和进化对于控制和抗击 2019 年冠状病毒病 (COVID-19) 大流行至关重要。目前,已经记录了超过 15000 种 SARS-CoV-2 单突变,这对诊断、疫苗、抗体疗法和药物的发展产生了重大影响。然而,人们对 SARS-CoV-2 的进化特征和总体趋势知之甚少。在这项工作中,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,宿主免疫反应通过 APOBEC 和 ADAR 基因编辑导致了近 65%的记录突变。此外,我们还表明,五岁以下儿童和老年人可能因对病毒感染的过度反应而面临 COVID-19 的高风险。此外,我们发现大洋洲和非洲的人群对 SARS-CoV-2 的感染反应明显比欧洲和亚洲更为强烈,这可能解释了为什么非裔美国人死于 COVID-19 的风险增加,除了他们因系统性健康和社会不平等而感染 COVID-19 的高风险。最后,我们的研究表明,对于两个具有相同起源的病毒基因组序列,它们的进化顺序可以从突变类型的比例来确定,即 C>T 多于 T>C。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ac/7599751/579f45065c14/viruses-12-01095-g001.jpg

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