Shanghai Public Health Clinical center AND Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Clinical Center for BioTherapy & Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Cell Infect Microbiol. 2022 Jul 14;12:941325. doi: 10.3389/fcimb.2022.941325. eCollection 2022.
() 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 strains varies and is clade-specific. EVA76, EVA89, EVA90, EVA91 and EVA92, the unconventional clade of strains, show unique codon usage pattern relative to the two conventional clades, including EVA71, CVA16, CVA6 and CVA10, Analyses of Effective Number of Codon (ENC), Correspondence Analysis (COA) and Parity Rule 2 (PR2), , revealed that the codon usage patterns of 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 . In addition, we have determined the codon usage compatibility of potential hosts for strains using codon adaptation index (CAI), relative codon deoptimization index (RCDI) and similarity index (SiD) analyses, and found that 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 clades associated with their host range, transmission and pathogenicity.
肠道病毒 71 型等多种病毒引起手足口病（HFMD），严重威胁婴幼儿健康。研究病毒与其宿主间的密码子使用偏好具有重要的基础理论价值和实际应用价值。本研究通过考察多个密码子使用参数，发现肠道病毒 71 型各毒株间的密码子使用偏好存在差异，且具有谱系特异性。EVA76、EVA89、EVA90、EVA91 和 EVA92 等非常规谱系的肠道病毒 71 型毒株与包括 EVA71、CVA16、CVA6 和 CVA10 在内的两个常规谱系相比，具有独特的密码子使用模式。有效密码子数（ENC）、对应分析（COA）和 PR2 分析结果表明，突变压力和自然选择共同影响肠道病毒 71 型各毒株的密码子使用偏好。基于中性分析，我们确定了自然选择在肠道病毒 71 型密码子使用偏好形成中的主导作用。此外，我们通过密码子适应指数（CAI）、相对密码子简并度指数（RCDI）和相似指数（SiD）分析，确定了不同谱系肠道病毒 71 型潜在宿主的密码子使用兼容性，发现不同谱系的肠道病毒 71 型在宿主间具有特定的密码子适应模式。最后，我们通过实验证实了非常规谱系独特的密码子使用模式影响其在人细胞系中的蛋白表达水平。综上，本研究明确了不同谱系肠道病毒 71 型独特的密码子使用偏好与其宿主范围、传播和致病性相关。
