Non-optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts
Non-optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts
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DOI：
10.1111/febs.15835
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发表时间：
2021-04-07
期刊：
影响因子：
5.4
通讯作者：
Frenkel-Morgenstern, Milana
中科院分区：
文献类型：
--
作者：
Carmi, Gon;Gorohovski, Alessandro;Frenkel-Morgenstern, Milana
流行的动物冠状病毒偶尔会感染人类。SARS-CoV-2是目前全球爆发的COVID-19的罪魁祸首，截至2021年1月下旬，已导致2 112 844人死亡。我们比较了496种病毒的遗传密码偏好，包括34种冠状病毒和242种相应的宿主，以发现区分单一和“混杂”多宿主感染病毒的模式。基于密码子使用偏好评分，与单宿主病毒相比，混杂病毒明显使用非最佳密码子，即涉及与反密码子“摆动”结合的密码子。计算所有病毒和宿主的密码子适应指数（CAI）和有效密码子数（ENC）。与单宿主病毒相比，混杂病毒对宿主的适应程度较低（p值= 4.392e-11）。所有冠状病毒都利用非最佳密码子感染多个宿主。我们发现，病毒编码序列开头的非最优密码子偏好可提高病毒蛋白在宿主体内的翻译效率。最后，冠状病毒在很大程度上缺乏内源性RNA降解基序，从而增加了病毒mRNA负担和感染负荷。综上所述，我们发现混合感染的冠状病毒更倾向于使用非最佳密码子来去除其RNA的降解基序，并显著提高其病毒RNA的产生率。
Circulating animal coronaviruses occasionally infect humans. The SARS-CoV-2 is responsible for the current worldwide outbreak of COVID-19 that has resulted in 2 112 844 deaths as of late January 2021. We compared genetic code preferences in 496 viruses, including 34 coronaviruses and 242 corresponding hosts, to uncover patterns that distinguish single- and 'promiscuous' multiple-host-infecting viruses. Based on a codon usage preference score, promiscuous viruses were shown to significantly employ nonoptimal codons, namely codons that involve 'wobble' binding to anticodons, as compared to single-host viruses. The codon adaptation index (CAI) and the effective number of codons (ENC) were calculated for all viruses and hosts. Promiscuous viruses were less adapted hosts vs single-host viruses (P-value = 4.392e-11). All coronaviruses exploit nonoptimal codons to infect multiple hosts. We found that nonoptimal codon preferences at the beginning of viral coding sequences enhance the translational efficiency of viral proteins within the host. Finally, coronaviruses lack endogenous RNA degradation motifs to a significant degree, thereby increasing viral mRNA burden and infection load. To conclude, we found that promiscuously infecting coronaviruses prefer nonoptimal codon usage to remove degradation motifs from their RNAs and to dramatically increase their viral RNA production rates.