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Clinical Epigenetics

, 7:103

First Online: 24 September 2015Received: 24 July 2015Accepted: 17 September 2015

Abstract

With the development of effective combined anti-retroviral therapy cART, there is significant reduction in deaths associated with human immunodeficiency virus type 1 HIV-1 infection. However, the complete cure of HIV-1 infection is difficult to achieve without the elimination of latent reservoirs which exist in the infected individuals even under cART regimen. These latent reservoirs established during early infection have long life span, include resting CD4 T cells, macrophages, central nervous system CNS resident macrophage-microglia, and gut-associated lymphoid tissue-macrophages, and can actively produce virus upon interruption of the cART. Several epigenetic and non-epigenetic mechanisms have been implicated in the regulation of viral latency. Epigenetic mechanisms such as histone post translational modifications e.g., acetylation and methylation and DNA methylation of the proviral DNA and microRNAs are involved in the establishment of HIV-1 latency. The better understanding of epigenetic mechanisms modulating HIV-1 latency could give clues for the complete eradication of these latent reservoirs. Several latency-reversing agents LRA have been found effective in reactivating HIV-1 reservoirs in vitro, ex vivo, and in vivo. Some of these agents target epigenetic modifications to elicit viral expression in order to kill latently infected cells through viral cytopathic effect or host immune response. These therapeutic approaches aimed at achieving a sterilizing cure elimination of HIV-1 from the human body. In the present review, we will discuss our current understanding of HIV-1 epigenomics and how this information can be moved from the laboratory bench to the patient’s bedside.

KeywordsHIV-1 Epigenetics Latency Histone modifications CD4 T cells Monocyte-macrophage Microglia MicroRNAs AbbreviationsAIDSacquired immune deficiency syndrome

BRD4bromodomain-containing protein 4

cARTeffective combined anti-retroviral therapy

CNScentral nervous system

CRFschromatin reassembly factors

CTIP2COUP-TF interacting protein 2

CTLscytotoxic T lymphocytes

DNMTDNA methyltransferase

DNMTiDNA methyltransferase inhibitor

DSFdisulfiram

EZH2enhancer of zeste homolog 2

FDAfood and drug administration

GALTgut associated lymphoid tissue

HAThistone acetyltransferase

HDAChistone deacetylase

HDACiHDAC inhibitor

HIV-1human immunodeficiency virus type 1

HMThistone lysine methyltransferase

HMTihistone methyltransferase inhibitor

ILinterleukin

INintegrase

LRAlatency reversing  agent

LEDGF-p75lens epithelium-derived growth factor

LSFlate SV40 factor

LTRlong terminal repeat

MBD2methyl-CpG binding domain protein 2

MDMmonocyte derived macrophages

NF-kBnuclear factor kappa B

PBMCperipheral blood mononuclear cells

PICpre-integration complex

PKCprotein kinase C

PRC2polycomb repressive complex 2

PTEbpositive transcription elongation factor b

TItranscriptional interference

VPAvalproic acid

WHOWorld Health Organization

YY1ying-yang 1

Amit Kumar and Gilles Darcis contributed equally to this work.

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Author: Amit Kumar - Gilles Darcis - Carine Van Lint - Georges Herbein

Source: https://link.springer.com/







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