Enterovirus A Shows Unique Patterns of Codon Usage Bias in Conventional Versus Unconventional Clade.
Enterovirus A Shows Unique Patterns of Codon Usage Bias in Conventional Versus Unconventional Clade.
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DOI：
10.3389/fcimb.2022.941325
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发表时间：
2022
影响因子：
5.7
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中科院分区：
文献类型：
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肠道病毒A（EV-A）种可引起手足口病（HFMD），威胁幼儿的健康。了解病毒与宿主之间的密码子使用模式具有重要的理论意义和应用价值。在这里，通过检查多个密码子使用参数，我们发现EV-A毒株之间的密码子使用偏好是不同的，并且是分支特异性的。EVA 76、EVA 89、EVA 90、EVA 91和EVA 92是EV-A的非常规进化枝，相对于EVA 71、CVA 16、CVA 6和CVA 10等两个常规进化枝，EVA 76、EVA 89、EVA 90、EVA 91和EVA 92具有独特的密码子使用模式。揭示了EV-A病毒株的密码子使用模式是由突变压力和自然选择形成的。基于中性分析，我们确定了自然选择在EV-A密码子使用偏性形成中的主导作用。此外，我们还利用密码子适应指数（CAI）、相对密码子去优化指数（RCDI）和相似性指数（SiD）分析了EV-A病毒潜在宿主的密码子使用相容性，发现EV-A病毒在不同进化枝中表现出宿主特异性密码子适应模式。最后，我们证实了非常规进化枝的独特密码子使用模式影响人类细胞系中的蛋白质表达水平。总之，我们确定了不同EV-A进化枝中密码子使用偏好的新特征，这些特征与它们的宿主范围、传播和致病性相关。
Enterovirus A (EV-A) species cause hand, foot and mouth disease (HFMD), threatening the health of young children. Understanding the mutual codon usage pattern of the virus and its host(s) has fundamental and applied values. Here, through examining multiple codon usage parameters, we found that the codon usage bias among EV-A strains varies and is clade-specific. EVA76, EVA89, EVA90, EVA91 and EVA92, the unconventional clade of EV-A strains, show unique codon usage pattern relative to the two conventional clades, including EVA71, CVA16, CVA6 and CVA10, etc. Analyses of Effective Number of Codon (ENC), Correspondence Analysis (COA) and Parity Rule 2 (PR2), etc., revealed that the codon usage patterns of EV-A strains are shaped by mutation pressure and natural selection. Based on the neutrality analysis, we determined the dominant role of natural selection in the formation of the codon usage bias of EV-A. In addition, we have determined the codon usage compatibility of potential hosts for EV-A strains using codon adaptation index (CAI), relative codon deoptimization index (RCDI) and similarity index (SiD) analyses, and found that EV-A showed host-specific codon adaptation patterns in different clades. Finally, we confirmed that the unique codon usage pattern of the unconventional clade affected protein expression level in human cell lines. In conclusion, we identified novel characteristics of codon usage bias in distinct EV-A clades associated with their host range, transmission and pathogenicity.