HDAC inhibitors stimulate viral transcription by multiple mechanisms.

Abstract

BACKGROUND:

The effects of histone deacetylase inhibitor (HDACi) treatment on SV40 transcription and replication were determined by monitoring the levels of early and late expression, the extent of replication, and the percentage of SV40 minichromosomes capable of transcription and replication following treatment with sodium butyrate (NaBu) and trichostatin A (TSA).

RESULTS:

The HDACi treatment was found to maximally stimulate early transcription at early times and late transcription at late times through increased numbers of minichromosomes which carry RNA polymerase II (RNAPII) transcription complexes and increased occupancy of the transcribing minichromosomes by RNAPII. HDACi treatment also partially relieved the normal down-regulation of early transcription by T-antigen seen later in infection. The increased recruitment of transcribing minichromosomes at late times was correlated to a corresponding reduction in SV40 replication and the percentage of minichromosomes capable of replication.

CONCLUSION:

These results suggest that histone deacetylation plays a critical role in the regulation of many aspects of an SV40 lytic infection.

• Authors: Lata Balakrishnan, Barry Milavetz
• Journal: Virology journal (Virol J) Vol. 5 Pg. 43 (Mar 19 2008) ISSN: 1743-422X [Electronic] England
• PMID: 18353181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Butyrates
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Viral Proteins
• trichostatin A
• RNA Polymerase II

Topics

• Animals
• Butyrates (pharmacology)
• Cell Line
• Chromosomes (genetics)
• Gene Expression Regulation, Viral (drug effects)
• Histone Deacetylase Inhibitors
• Hydroxamic Acids (pharmacology)
• RNA Polymerase II (genetics, metabolism)
• Simian virus 40 (drug effects, genetics, physiology)
• Transcription, Genetic (drug effects)
• Viral Proteins (genetics, metabolism)
• Virus Replication (drug effects)