Accessible Requires Authentication Published by De Gruyter October 31, 2017

Therapeutic strategies to fight HIV-1 latency: progress and challenges

Sello Lebohang Manoto, Lebogang Thobakgale, Rudzani Malabi, Charles Maphanga, Saturnin Ombinda-Lemboumba and Patience Mthunzi-Kufa
From the journal Biologia

Abstract

The life-long persistence of human immunodeficiency virus type-1 (HIV-1) in latent reservoirs is a major hurdle in the eradication of HIV-1, even though highly active antiretroviral therapy (HAART) can be effective in reducing the plasma HIV-1 RNA to less than 50 copies per mL, which is below the detection limit of most clinical assays. In the latent reservoirs the provirus is integrated in the host genome but does not actively replicate and thus is not inhibited by HAART or recognized by the host immune system. There has been increasing scientific interest and investment into research towards HIV cure due to the challenges and limitation of life long treatment. The various strategies that have been developed aim to activate gene expression in HIV latent cells which might lead to the elimination of the virus by HAART or the immune system. In this review we discuss latency and therapeutic approaches that are being evaluated to eradicate HIV latently infected cells to overcome the burden of life long HAART. In addition, we explore the possibility of delivering HAART in latently infected cells using femtosecond laser pulses, a topic closely studied in our research.

Acknowledgements

The authors thank the Council for Scientific and Industrial Research and the Department of Science and Technology of South Africa for providing support.

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Abbreviations

AIDS

acquired immune deficiency syndrome

AP1

activator protein 1

BAF

BRG-Brahma associated factors

BAFi

BAF inhibitors

bNAbs

broadly neutralizing antibodies

BRD

bromodomain

BET

bromodomain and extraterminal domain

CDK9

cyclin dependent kinase 9

CNS

central nervous system

COUP

chicken ovalbumin upstream promoter

CRISPR

clustered regularly interspaced short palindromic repeats

CTLs

cytotoxic T lymphocytes

CycT1

cyclin T1

DNMTI

DNA methyltransferase inhibitors

HAART

highly active antiretroviral therapy

HDACi

histone deacetylase inhibitors

HDACs

histone deacetylases

HEXIM-1

HMBA-induced protein 1

HMBA

hexamethylene bisacetamide

HMTI

histone methyltransferase inhibitors

HMTS

histone methyltransferases

HSV

Herpes Simplex Virus

I?B-α

inhibitor of kappa B alpha

IL

interleukin

Jak

Janus kinase

LTR

long terminal repeat

MBD2

methyl-CpG binding domain protein 2

NF1

nuclear factor 1

NFAT

nuclear factor of activated T cells

NFκB

nuclear factor kappa B

PD1

programmed cell death protein 1

PKC

protein kinase C

p-TEFb

positive transcription elongation factor b

siRNA

small interfering RNA

SP1

specificity protein 1

STAT

signal transducer and activator of transcription

TCF-1α

transcription factor 1 alpha

TK

thymidine kinase

TLRs

toll-like receptors

UBP-1

upstream binding protein 1

USF

upstream stimulatory factor

Received: 2017-5-12
Accepted: 2017-10-22
Published Online: 2017-10-31
Published in Print: 2017-10-26

© 2017 Institute of Molecular Biology, Slovak Academy of Sciences