June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
OCT4 and YY1 transcription factors regulate gene expression of an adenoviral ocular pathogen
Author Affiliations & Notes
  • Ting Su
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, China
  • Ashrafali Mohamed Ismail
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Meeta Mistry
    Biostatistics, Harvard University T H Chan School of Public Health, Boston, Massachusetts, United States
  • Donald Seto
    School of Systems Biology, George Mason University, Fairfax, Virginia, United States
  • David W. Dyer
    Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • James Chodosh
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Jaya Rajaiya
    Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ting Su, None; Ashrafali Mohamed Ismail, None; Meeta Mistry, None; Donald Seto, None; David Dyer, None; James Chodosh, None; Jaya Rajaiya, None
  • Footnotes
    Support  National Institutes of Health grants EY013124, EY021558, and EY014104, an unrestricted grant to the Department of Ophthalmology, Harvard Medical School from Research to Prevent Blindness, Inc., New York, New York; and the Massachusetts Lions Eye Research Fund
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1954. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ting Su, Ashrafali Mohamed Ismail, Meeta Mistry, Donald Seto, David W. Dyer, James Chodosh, Jaya Rajaiya; OCT4 and YY1 transcription factors regulate gene expression of an adenoviral ocular pathogen. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1954.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : There are about 20 million ocular adenoviral cases per year in the United States. Epidemic keratoconjunctivitis (EKC) is the most highly contagious and most severe of these. EKC manifests with acute membranous keratoconjunctivitis and delayed-onset of corneal stromal infiltrates. Transcription factors (TFs) are sequence-specific DNA binding proteins. As intracellular parasites, viruses hijack host cellular proteins, including TFs, to control their gene expression and replication. We investigated the role of host TFs in the transcriptional regulation of a major EKC pathogen - human adenovirus species D type 37 (HAdV-D37).

Methods : We first performed in silico TRANSFAC database analysis to identify TF candidates for binding to the HAdV-D37 genome. Next, chromatin immunoprecipitation and high-throughput sequencing (ChIP-Seq) were performed in virus-infected A549 cells, including the TF YY1, previously reported to bind E1A. From the high-throughput sequencing reads (HiSeq 2500 system, illumina), motif analysis was performed, and the specific TF-viral DNA binding sites were validated by electrophoretic mobility shift assays (EMSA). Gene expression was studied in the setting of both TF-siRNA knockdown and overexpression, using RT-qPCR for viral transcripts spanning the whole genome.

Results : In silico analysis showed OCT4 as the TF with greatest binding affinity for the HAdV-D37 genome. By ChIP-Seq analysis, OCT4 and YY1 were shown to directly bind the viral DNA motifs, ATTTGCAT and CGCCATCTT, respectively, present in the non-coding regions of the inverted terminal repeat (ITR) and adjacent to E4 target genes. Both OCT4 and YY1 were shown to repress E3 (immune evasion genes) expression. Additionally, YY1 knockdown upregulated viral early gene expression, including E1B, E2A, and E2B.

Conclusions : OCT4 and YY1 directly bind to HAdV-D37 and downregulate E3 gene expression, potentially modulating host immune responses to infection. Our findings provide novel functions for non-coding viral DNA; in depth understanding of viral gene expression offers a unique perspective to treatment of ocular viral disease.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×