Epigenetic control of HIV-1 post integration latency: Implications for therapy

CD4+ T cells; Epigenetics; Histone modifications; HIV-1; Latency; Microglia; MicroRNAs; Monocyte/macrophage; CD4+ T lymphocyte; DNA methylation; Human immunodeficiency virus 1; Review

Abstract :

[en] 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. © 2015 Kumar et al.

Disciplines :

Immunology & infectious disease

Author, co-author :

Kumar, A. ^✱; Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon, Hôpital Saint-Jacques, 2 place Saint-Jacques, Besançon cedex, France

DARCIS, Gilles ^✱; Centre Hospitalier Universitaire de Liège - CHU > Service des maladies infectieuses - médecine interne

Van Lint, C.; Service of Molecular Virology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles (ULB), 12 Rue des Profs Jeener et Brachet, Gosselies, Belgium

Herbein, G.; Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon, Hôpital Saint-Jacques, 2 place Saint-Jacques, Besançon cedex, France

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Epigenetic control of HIV-1 post integration latency: Implications for therapy

Publication date :

2015

Journal title :

Clinical Epigenetics

ISSN :

1868-7075

eISSN :

1868-7083

Publisher :

Springer Verlag

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 17 January 2018

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