人腺病毒 D 种 E1A CR3 的趋异进化。
Divergent Evolution of E1A CR3 in Human Adenovirus Species D.
机构信息
Department of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
出版信息
Viruses. 2019 Feb 8;11(2):143. doi: 10.3390/v11020143.
Adenovirus E1A is the first viral protein expressed during infection. E1A controls critical aspects of downstream viral gene expression and cell cycle deregulation, and its function is thought to be highly conserved among adenoviruses. Various bioinformatics analyses of E1A from 38 human adenoviruses of species D (HAdV-D), including likelihood clade model partitioning, provided highly significant evidence of divergence of HAdV-Ds into two distinct groups for the conserved region 3 (CR3), present only in the E1A 13S isoform. This variance within E1A 13S of HAdV-Ds was not found in any other human adenovirus (HAdV) species. By protein sequence and structural analysis, the zinc finger motif of E1A CR3, previously shown as critical for transcriptional activation, showed the greatest differences. Subsequent codon usage bias analysis revealed substantial divergence in E1A 13S between the two groups of HAdV-Ds, suggesting that these two sub-groups of HAdV-D evolved under different cellular conditions. Hence, HAdV-D E1A embodies a previously unappreciated evolutionary divergence among HAdVs.
腺病毒 E1A 是感染过程中最早表达的病毒蛋白。E1A 控制下游病毒基因表达和细胞周期失调的关键方面，其功能被认为在腺病毒中高度保守。对来自种 D 的 38 种人类腺病毒（HAdV-D）的 E1A 进行了各种生物信息学分析，包括似然聚类模型分区，为 CR3 （仅存在于 E1A 13S 异构体中）的保守区 3 提供了高度显著的证据，表明 HAdV-D 分为两个截然不同的组。这种 HAdV-D 的 E1A 13S 内的变异在任何其他人类腺病毒（HAdV）种中都没有发现。通过蛋白质序列和结构分析，先前显示对转录激活至关重要的 E1A CR3 锌指基序显示出最大的差异。随后的密码子使用偏性分析显示，这两组 HAdV-D 之间的 E1A 13S 存在明显的差异，表明这两组 HAdV-D 在不同的细胞条件下进化。因此，HAdV-D E1A 体现了 HAdV 之间以前未被认识到的进化分歧。
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