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Review
. 2018 Sep;34(9):739-759.
doi: 10.1089/AID.2018.0118. Epub 2018 Aug 28.

Barriers for HIV Cure: The Latent Reservoir

Sergio Castro-Gonzalez  1 , Marta Colomer-Lluch  2 , Ruth Serra-Moreno  1
Affiliations
Review

Barriers for HIV Cure: The Latent Reservoir

Sergio Castro-Gonzalez et al. AIDS Res Hum Retroviruses. 2018 Sep.

Abstract

Thirty-five years after the identification of HIV-1 as the causative agent of AIDS, we are still in search of vaccines and treatments to eradicate this devastating infectious disease. Progress has been made in understanding the molecular pathogenesis of this infection, which has been crucial for the development of the current therapy regimens. However, despite their efficacy at limiting active viral replication, these drugs are unable to purge the latent reservoir: a pool of cells that harbor transcriptionally inactive, but replication-competent HIV-1 proviruses, and that represent the main barrier to eradicate HIV-1 from affected individuals. In this review, we discuss advances in the field that have allowed a better understanding of HIV-1 latency, including the diverse cell types that constitute the latent reservoir, factors influencing latency, tools to study HIV-1 latency, as well as current and prospective therapeutic approaches to target these latently infected cells, so a functional cure for HIV/AIDS can become a reality.

Keywords: HIV; block and lock; latency; persistent infection; shock and kill; viral reservoirs.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

<b>FIG. 1.</b>
FIG. 1.
Factors influencing the establishment and maintenance of latency. (A) Effects of chromatin condensation status and epigenetic modifications in the repression (top) or activation (bottom) of HIV-1 transcription. (B) Representation of scenarios for transcriptional interference. Top: when the HIV-1 provirus is in the same orientation as a highly expressed cellular gene. Bottom: when the provirus and the cellular host gene have opposite orientations. Color images are available online at www.liebertpub.com/aid
<b>FIG. 2.</b>
FIG. 2.
Current therapeutic strategies to eradicate the HIV-1 latent reservoirs. Schematic representation of the molecules targeted by (1) latency-reversing agents in shock and kill approaches (left panel), (2) latency-promoting agents in block and lock approaches (central panel), and (3) CRISPR-mediated DNA scission techniques (right panel). (A) Gene editing tools to reactivate proviruses. (B) Gene editing tools to excise HIV-1 proviruses. CRISPR, clustered, regularly interspaced short palindromic repeat. Color images are available online at www.liebertpub.com/aid
See this image and copyright information in PMC

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