Targeting HIV latency: Pharmacologic strategies toward eradication

Sifei Xing, Robert F Siliciano

Research output: Contribution to journalArticle

Abstract

The latent reservoir for HIV-1 in resting CD4+ T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations.

Original languageEnglish (US)
Pages (from-to)541-551
Number of pages11
JournalDrug Discovery Today
Volume18
Issue number11-12
DOIs
StatePublished - Jun 2013

Fingerprint

HIV-1
HIV
Histones
Highly Active Antiretroviral Therapy
DNA Methylation
Epigenomics
Methylation
Disease Progression
Limit of Detection
Transcription Factors
Pharmacology
T-Lymphocytes

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Targeting HIV latency : Pharmacologic strategies toward eradication. / Xing, Sifei; Siliciano, Robert F.

In: Drug Discovery Today, Vol. 18, No. 11-12, 06.2013, p. 541-551.

Research output: Contribution to journalArticle

@article{7404cfbb1c5b4af3bc239efe67a94f5a,
title = "Targeting HIV latency: Pharmacologic strategies toward eradication",
abstract = "The latent reservoir for HIV-1 in resting CD4+ T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations.",
author = "Sifei Xing and Siliciano, {Robert F}",
year = "2013",
month = "6",
doi = "10.1016/j.drudis.2012.12.008",
language = "English (US)",
volume = "18",
pages = "541--551",
journal = "Drug Discovery Today",
issn = "1359-6446",
publisher = "Elsevier Limited",
number = "11-12",

}

TY - JOUR

T1 - Targeting HIV latency

T2 - Pharmacologic strategies toward eradication

AU - Xing, Sifei

AU - Siliciano, Robert F

PY - 2013/6

Y1 - 2013/6

N2 - The latent reservoir for HIV-1 in resting CD4+ T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations.

AB - The latent reservoir for HIV-1 in resting CD4+ T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations.

UR - http://www.scopus.com/inward/record.url?scp=84878873135&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878873135&partnerID=8YFLogxK

U2 - 10.1016/j.drudis.2012.12.008

DO - 10.1016/j.drudis.2012.12.008

M3 - Article

C2 - 23270785

AN - SCOPUS:84878873135

VL - 18

SP - 541

EP - 551

JO - Drug Discovery Today

JF - Drug Discovery Today

SN - 1359-6446

IS - 11-12

ER -