Abstract
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.
Highlights
Human adenoviruses (HAdVs) belong to the genus Mastadenovirus within the Adenoviridae family, and comprise seven species, human adenovirus (HAdV)-A to HAdV-G
We previously found that proteotyping, a novel bioinformatics tool used to elucidate amino acid signatures, [5,40] was invaluable for understanding intra-species conservation within hypervariable E3 regions of human adenoviruses of species D (HAdV-D) [6], resulting in the identification of unique proteotypes having potentially unique functional features [41]
To look at the conserved region 3 (CR3) region of E1A 13S, we applied proteotyping to these 60 HAdVs
Summary
Human adenoviruses (HAdVs) belong to the genus Mastadenovirus within the Adenoviridae family, and comprise seven species, HAdV-A to HAdV-G. Recombination pressure was found to be most prominent in the major structural components of the viral capsid, the penton base, hexon, and fiber proteins, along with the three E3 CR1 open reading frames (ORFs). These regions are the most hypervariable among all the ORFs in the HAdV-D genome. These insights were possible only through continued efforts to fully characterize newly identified adenoviruses through whole-genome sequencing [5,10].
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