SARS-CoV-2 Entry Related Viral and Host Genetic Variations: Implications on COVID-19 Severity, Immune Escape, and Infectivity.
SARS-CoV-2 Entry Related Viral and Host Genetic Variations: Implications on COVID-19 Severity, Immune Escape, and Infectivity.
复制标题
DOI：
10.3390/ijms22063060
复制
发表时间：
2021-03-17
影响因子：
5.6
通讯作者：
Wang SF
中科院分区：
文献类型：
--
作者：
Huang SW;Wang SF
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）已经进化到在不同地理区域的基因组中显示出特定的遗传多样性模式。病毒的这些变异和人群中的遗传变异可以决定病毒的传播能力和2019冠状病毒病（COVID-19）的严重程度。人类群体中的遗传变异和免疫差异可能是病毒进化的驱动力。最近出现的SARS-CoV-2变体在刺突(S)糖蛋白的受体结合域显示出几个突变，并有助于免疫逃逸和与血管紧张素1转换酶2 （ACE2）的结合增强。由于ACE2和跨膜蛋白酶丝氨酸2 （TMPRSS2）在SARS-CoV-2进入细胞中发挥重要作用，这些宿主进入相关蛋白的遗传变异可能是SARS-CoV-2 S糖蛋白阳性选择的驱动力。树突状或肝/淋巴细胞特异性细胞间粘附分子(ICAM)-3-抓取非整合素也被认为在几种病原体中发挥重要作用。这些宿主蛋白的遗传变异可能影响对SARS-CoV-2的易感性。本文综述了病毒S糖蛋白和关键宿主蛋白遗传变异影响的最新研究进展，旨在更好地了解病毒的传播和发病机制，并为开发疫苗/抗病毒药物和精准医疗策略提供更广泛的见解，特别是针对具有遗传风险变异的高危人群。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to display particular patterns of genetic diversity in the genome across geographical regions. These variations in the virus and genetic variation in human populations can determine virus transmissibility and coronavirus disease 2019 (COVID-19) severity. Genetic variations and immune differences in human populations could be the driving forces in viral evolution. Recently emerged SARS-CoV-2 variants show several mutations at the receptor binding domain in the spike (S) glycoprotein and contribute to immune escape and enhanced binding with angiotensin 1-converting enzyme 2 (ACE2). Since ACE2 and transmembrane protease serine 2 (TMPRSS2) play important roles in SARS-CoV-2 entry into the cell, genetic variation in these host entry-related proteins may be a driving force for positive selection in the SARS-CoV-2 S glycoprotein. Dendritic or liver/lymph cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin is also known to play vital roles in several pathogens. Genetic variations of these host proteins may affect the susceptibility to SARS-CoV-2. This review summarizes the latest research to describe the impacts of genetic variation in the viral S glycoprotein and critical host proteins and aims to provide better insights for understanding transmission and pathogenesis and more broadly for developing vaccine/antiviral drugs and precision medicine strategies, especially for high risk populations with genetic risk variants.