Experimental study demonstrates that suberoylanilide hydroxamic acid reactivates latent HIV in primary T cells, suggesting potential utility in purging persistent viral reservoirs.
Key Points
Determine whether the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) can reactivate latent HIV proviruses and identify the underlying transcriptional and signaling mechanisms.
Treated chronically infected cell lines and primary cells with SAHA to assess latent HIV reactivation.
Evaluated P-TEFb release, viral promoter recruitment, and PI3K/Akt pathway activation using single-cell phosphoprotein flow cytometry in T-cell subsets.
Tested SAHA-mediated induction of viral replication using peripheral blood mononuclear cells isolated from patients successfully treated with HAART.
SAHA induced HIV reactivation from latency in both chronically infected cell lines and primary CD4+ T cells.
Reactivation required activation of the PI3K/Akt signaling pathway across memory T-cell subsets, triggering the release and recruitment of transcription factor P-TEFb to the HIV promoter.
SAHA stimulated viral replication in peripheral blood mononuclear cells derived from virally suppressed, HAART-treated individuals.