The multifaceted nature of HIV latency
Caroline Dufour, … , Rémi Fromentin, Nicolas Chomont
Caroline Dufour, … , Rémi Fromentin, Nicolas Chomont
Published July 1, 2020
Citation Information: J Clin Invest. 2020;130(7):3381-3390. https://doi.org/10.1172/JCI136227.
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Review Series

The multifaceted nature of HIV latency

Abstract

Although antiretroviral therapies (ARTs) potently inhibit HIV replication, they do not eradicate the virus. HIV persists in cellular and anatomical reservoirs that show minimal decay during ART. A large number of studies conducted during the past 20 years have shown that HIV persists in a small pool of cells harboring integrated and replication-competent viral genomes. The majority of these cells do not produce viral particles and constitute what is referred to as the latent reservoir of HIV infection. Therefore, although HIV is not considered as a typical latent virus, it can establish a state of nonproductive infection under rare circumstances, particularly in memory CD4+ T cells, which represent the main barrier to HIV eradication. While it was originally thought that the pool of latently infected cells was largely composed of cells harboring transcriptionally silent genomes, recent evidence indicates that several blocks contribute to the nonproductive state of these cells. Here, we describe the virological and immunological factors that play a role in the establishment and persistence of the pool of latently infected cells and review the current approaches aimed at eliminating the latent HIV reservoir.

Authors

Caroline Dufour, Pierre Gantner, Rémi Fromentin, Nicolas Chomont

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Figure 1

Distinguishing HIV persistence and HIV latency.

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Distinguishing HIV persistence and HIV latency. During untreated HIV inf...
During untreated HIV infection, the majority of infected cells are short-lived: HIV viremia is sustained by a dynamic process involving continuous rounds of de novo infection. Initiation of ART (blue dashed lines) leads to a dramatic reduction in the levels of viral replication and in the frequency of infected cells. Residual viremia persists and can originate from low levels of ongoing replication or, more likely, from the continuous production of viral particles from stable reservoirs. The majority of infected cells in PLHIV on ART do not produce viral particles and are defined as latently infected cells. Although the production of spliced transcripts or viral proteins is rare, a relatively large fraction of these cells produce short, abortive viral transcripts. Complete silencing of HIV genomes may also occur when epigenetic regulators repress the LTR transcriptional activity.