Back to Search
Start Over
Unique characteristics of histone deacetylase inhibitors in reactivation of latent HIV-1 in Bcl-2-transduced primary resting CD4+ T cells
- Source :
- The Journal of antimicrobial chemotherapy. 69(1)
- Publication Year :
- 2013
-
Abstract
- The latent reservoir for HIV-1 in resting memory CD4+ T cells is a major barrier to eradication. In vitro models involving transformed cell lines have been used to search for small molecules that reactivate latent HIV-1. Histone deacetylase (HDAC) inhibitors can reverse HIV-1 latent infection. Most studies on HDAC inhibitors have been performed in cell line models that differ in important aspects from the resting CD4+ T cells that harbour latent HIV-1 in vivo. Therefore, we evaluated the potency and kinetics of HDAC inhibitors in a primary cell model of HIV-1 latency that involves resting CD4+ T cells.A green fluorescent protein (GFP)-expressing reporter virus NL4-3-Δ6-drGFP was used to generate latent infection in Bcl-2-transduced primary CD4+ T cells. Seventeen HDAC inhibitors were tested in this primary cell model. The effects of these HDAC inhibitors on the reactivation of latent HIV-1 were determined and compared with anti-CD3 and anti-CD28 co-stimulation.In Bcl-2-transduced primary CD4+ T cells, short-term treatment with HDAC inhibitors resulted in very limited reactivation of latent HIV-1, while prolonged treatment greatly enhanced drug efficacy. The effects of HDAC inhibitors in reactivating latent HIV-1 correlated with their inhibitory effects on class I HDACs. Importantly, HIV-1 reactivated by HDAC inhibitors can quickly re-establish latent infection upon drug removal.We identified unique features of HDAC inhibitor-induced reactivation of latent HIV-1 in primary CD4+ T cells. Our findings may be useful for the design of eradication trials.
- Subjects :
- Microbiology (medical)
CD4-Positive T-Lymphocytes
medicine.drug_class
Green Fluorescent Proteins
Biology
Virus Replication
In vivo
Genes, Reporter
Virus latency
medicine
Humans
Pharmacology (medical)
Cytotoxicity
Vorinostat
Cells, Cultured
Original Research
Pharmacology
Staining and Labeling
Histone deacetylase inhibitor
T lymphocyte
medicine.disease
Molecular biology
In vitro
Virus Latency
Histone Deacetylase Inhibitors
Infectious Diseases
Cancer research
HIV-1
Virus Activation
Histone deacetylase
medicine.drug
Subjects
Details
- ISSN :
- 14602091
- Volume :
- 69
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of antimicrobial chemotherapy
- Accession number :
- edsair.doi.dedup.....4686929dbea549c119cdd5981fb84c60