COVID-19: The Effect of Host Genetic Variations on Host–Virus Interactions,Journal of Proteome Research

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COVID-19: The Effect of Host Genetic Variations on Host–Virus Interactions
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-12-10 , DOI: 10.1021/acs.jproteome.0c00637
Suvobrata Chakravarty _{1,

2}

Affiliation

Spurred into action by the COVID-19 pandemic, the global scientific community has, in a short of period of time, made astonishing progress in understanding and combating COVID-19. Given the known human protein machinery for (a) SARS-CoV-2 entry, (b) the host innate immune response, and (c) virus–host interactions (protein–protein and RNA–protein), the potential effects of human genetic variation in this machinery, which may contribute to clinical differences in SARS-CoV-2 pathogenesis and help determine individual risk for COVID-19 infection, are explored. The Genome Aggregation Database (gnomAD) was used to show that several rare germline exome variants of proteins in these pathways occur in the human population, suggesting that carriers of these rare variants (especially for proteins of innate immunity pathways) are at risk for severe symptoms (like the severe symptoms in patients who are known to be rare variant carriers), whereas carriers of other variants could have a protective advantage against infection. The occurrence of genetic variation is thus expected to motivate the experimental probing of natural variants to understand the mechanistic differences in SARS-CoV-2 pathogenesis from one individual to another.

中文翻译：

COVID-19：宿主基因变异对宿主与病毒相互作用的影响

在 COVID-19 大流行的推动下，全球科学界在短时间内在理解和抗击 COVID-19 方面取得了惊人的进展。鉴于已知的人类蛋白质机制（a）SARS-CoV-2进入，（b）宿主先天免疫反应，以及（c）病毒-宿主相互作用（蛋白质-蛋白质和RNA-蛋白质），人类遗传的潜在影响我们探讨了这种机制的变异，这可能导致 SARS-CoV-2 发病机制的临床差异，并有助于确定个体感染 COVID-19 的风险。基因组聚合数据库 (gnomAD) 用于显示这些途径中蛋白质的几种罕见种系外显子组变异存在于人群中，这表明这些罕见变异（尤其是先天免疫途径蛋白质）的携带者面临严重症状的风险（就像已知的罕见变异携带者患者的严重症状一样），而其他变异携带者可能具有针对感染的保护优势。因此，遗传变异的发生有望激发对自然变异的实验探索，以了解个体之间 SARS-CoV-2 发病机制的机制差异。

更新日期：2021-01-01

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