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Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
Published on: November 12, 2015
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Adenovirus E1A targets the DREF nuclear factor to regulate virus gene expression, DNA replication, and growth
Sandi Radko1, Maria Koleva1, Kris M D James2
1Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Journal of Virology
|September 12, 2014
Summary
Adenovirus E1A protein binds to DREF (ZBED1), a factor with a dual role in viral replication. DREF activates early viral gene expression but restricts adenovirus growth late in infection.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Adenovirus E1A protein is crucial for viral replication, modulating cellular and viral gene expression.
- E1A functions by interacting with cellular proteins, but its C-terminus remains poorly characterized.
- Identifying novel E1A binding partners can elucidate new mechanisms of viral control.
Purpose of the Study:
- To identify novel binding partners of the adenovirus E1A C-terminus.
- To investigate the role of the identified binding partner in adenovirus infection.
- To characterize the function of DREF (ZBED1) in the context of adenovirus replication.
Main Methods:
- Co-immunoprecipitation to identify E1A binding partners.
- siRNA-mediated knockdown to assess DREF function.
- Immunofluorescence microscopy to determine subcellular localization.
- Quantitative PCR and viral DNA copy number analysis to measure viral replication.
Main Results:
- DREF (ZBED1) was identified as a novel, direct binding partner of the adenovirus E1A C-terminus.
- DREF localizes to PML nuclear bodies and virus replication centers, with E1A influencing its distribution and SUMOylation.
- Knockdown of DREF enhanced adenovirus replication, viral DNA copy number, and overall virus yield late in infection.
- DREF was found at viral promoters with E1A, suggesting a role in early viral gene activation.
Conclusions:
- DREF is a novel binding partner of adenovirus E1A, impacting viral replication.
- DREF exhibits a dual role: activating early viral gene expression and restricting viral growth later in infection.
- E1A modulates DREF's localization and post-translational modification (SUMOylation).
- DREF represents a new target for understanding and potentially controlling adenovirus infection.
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