Depletion of latent HIV-1 infection in vivo: a proof-of-concept study

Abstract

SummaryBackground-Persistent infection in resting CD4+ Tcells prevents eradication of HIV-1. Since the chromatin remodeling enzyme histone deacetylase 1 (HDAC1) maintains latency of integrated HIV, we tested the ability of the HDAC inhibitor valproic acid to deplete persistent, latent infection in resting CD4 T cells.

Stable gene expression occurs from a minority of integrated HIV-1-based vectors: transcriptional silencing is present in the majority

“…Indeed, in a recent study, administrating the histone deacetylase inhibitor valproic acid to HIV-1-infected patients for 3 months reduced the size of the pool of latently infected cells but could not completely purge it. 47 Given that perturbation of epigenetic markers such as DNA methylation 48 and histone acetylation 49 are associated with malignancy, more research is required to study the effects of these agents on proviral gene expression.…”

Role of Downstream Elements in Transcriptional Regulation of the HIV-1 Promoter

“…Thus, studying the downstream region, especially in an integrated scenario to focus on DNAse I hypersensitive areas, can provide important cues that can extend our knowledge with respect to transcriptional activation in both active and latent proviral genome pools [59]. The attempts to purge the latent HIV-1 reservoir have included strategies that utilize cytokines like IL-6, IL-2, and TNFα to induce a global cellular activation [60][61][62][63]; HDAC1 inhibitors like valproic acid (VPA) and suberoyl anilide hydroxamic acid (SAHA) to induce transcription [64,65] all of which would have impact on the downstream region of the LTR; and inhibition of DNA methylation using 5-aza-2'deoxycytidine (aza-CdR) [66]. Newer approaches have shown an interest in a novel group of transcriptional regulators that control viral gene expression.…”

Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy

“…In this perspective, an ideal anti HIV therapy should include drugs that protect new cells from infection (i.e., HAART) as well as agents able to reduce the reservoir of infected cells. The first reservoir that has been identified consists of resting CD4 ϩ memory T lymphocytes, and most efforts were aimed at designing treatment strategies able to reduce them (11,26). Other reservoirs, however, and in particular M/M, are also involved in maintaining HIV infection in chronically treated patients and must be considered when protocols aimed at eradicating HIV infection are designed.…”