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HDAC inhibitors stimulate viral transcription by multiple mechanisms

Lata Balakrishnan1, Barry Milavetz

  • 1Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA. lbalakrishnan@medicine.nodak.edu

Virology Journal
|March 21, 2008
PubMed
Abstract

Insights

Histone deacetylase inhibitors (HDACi) enhance SV40 transcription by increasing minichromosome activity and RNA polymerase II (RNAPII) occupancy. However, this stimulation correlates with reduced SV40 replication, highlighting HDACi

Area of Science:

  • Molecular Biology
  • Virology
  • Epigenetics

Background:

  • Histone deacetylase inhibitors (HDACi) modulate gene expression through epigenetic mechanisms.
  • SV40 (Simian Virus 40) is a model system for studying viral transcription and replication.
  • Understanding HDACi effects on viral processes is crucial for antiviral strategies.

Purpose of the Study:

  • To investigate the impact of HDACi, specifically sodium butyrate (NaBu) and trichostatin A (TSA), on SV40 transcription and replication.
  • To determine how HDACi influences viral gene expression kinetics and DNA replication efficiency.

Main Methods:

  • Treatment of cells with HDAC inhibitors (NaBu and TSA).
  • Monitoring of SV40 early and late gene expression levels.
  • Quantification of SV40 DNA replication extent.
  • Assessment of SV40 minichromosomes capable of transcription and replication.

Main Results:

  • HDACi treatment maximally stimulated early SV40 transcription at early times and late transcription at late times.
  • Increased minichromosome numbers and RNA polymerase II (RNAPII) occupancy on transcribing minichromosomes were observed.
  • HDACi partially relieved T-antigen-mediated down-regulation of early transcription.
  • Increased transcription correlated with reduced SV40 replication and fewer replication-competent minichromosomes.

Conclusions:

  • Histone deacetylation is a critical regulator of SV40 lytic infection.
  • HDACi differentially impact SV40 transcription and replication.
  • Epigenetic modifications play a significant role in viral life cycles.

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