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Viruses 2019, 11(2), 143;

Divergent Evolution of E1A CR3 in Human Adenovirus Species D

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
Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, VA 22030, USA
Authors to whom correspondence should be addressed.
Present address: Molecular Virology Laboratory, Korea Zoonosis Research Institute, Jeonbuk 11, National University, Iksan, Korea.
Received: 16 January 2019 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 8 February 2019
(This article belongs to the Section Animal Viruses)
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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. View Full-Text
Keywords: adenovirus; E1A; viral evolution adenovirus; E1A; viral evolution

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Singh, G.; Ismail, A.M.; Lee, J.Y.; Ramke, M.; Lee, J.S.; Dyer, D.W.; Seto, D.; Rajaiya, J.; Chodosh, J. Divergent Evolution of E1A CR3 in Human Adenovirus Species D. Viruses 2019, 11, 143.

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