SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage
SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage
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DOI：
10.3389/fcell.2020.00831
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发表时间：
2020-08-20
影响因子：
5.5
通讯作者：
Diambra, Luis
中科院分区：
文献类型：
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作者：
Alonso, Andres Mariano;Diambra, Luis
严重急性呼吸系统综合症在世界各地迅速蔓延，并被世界卫生组织（卫生组织）宣布为大流行病。致病菌是一种新型冠状病毒（SARS-CoV-2），能有效感染肺细胞。本文主要研究了病毒蛋白合成的密码子组成及其与宿主蛋白合成的关系。我们的分析显示，SARS-CoV-2首选密码子在第三位的G或C核苷酸代表性较差，这一特征可能导致受感染细胞的trna池不平衡，严重影响宿主蛋白质合成。通过将这一观察结果与感染细胞的蛋白质组学数据相结合，我们观察到与高表达基因相关的宿主蛋白质的翻译率降低，并且它们共享病毒的密码子使用偏好。这些基因的功能分析表明，这种上位机制有助于了解该病毒如何逃避免疫反应以及由于病毒复制而产生的一些有害附带效应的病因。通过这种方式，我们的发现有助于了解SARS-CoV-2的发病机制，并可用于基于减毒活疫苗策略的疫苗设计。
Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.