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Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection

Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and that can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a res...

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Autores principales: Lau, Chuen-Yen, Adan, Matthew A., Maldarelli, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708047/
https://www.ncbi.nlm.nih.gov/pubmed/34960781
http://dx.doi.org/10.3390/v13122512
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author Lau, Chuen-Yen
Adan, Matthew A.
Maldarelli, Frank
author_facet Lau, Chuen-Yen
Adan, Matthew A.
Maldarelli, Frank
author_sort Lau, Chuen-Yen
collection PubMed
description Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and that can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a reservoir of long-lived latently infected cells and their progeny. This proviral landscape undergoes change over time on ART. One of the forces driving change in the landscape is the clonal expansion of infected CD4 T cells, which presents a key obstacle to HIV eradication. Potential mechanisms of clonal expansion include general immune activation, antigenic stimulation, homeostatic proliferation, and provirus-driven clonal expansion, each of which likely contributes in varying, and largely unmeasured, amounts to maintaining the reservoir. The role of clinical events, such as infections or neoplasms, in driving these mechanisms remains uncertain, but characterizing these forces may shed light on approaches to effectively eradicate HIV. A limited number of individuals have been cured of HIV infection in the setting of bone marrow transplant; information from these and other studies may identify the means to eradicate or control the virus without ART. In this review, we describe the mechanisms of HIV-1 persistence and clonal expansion, along with the attempts to modify these factors as part of reservoir reduction and cure strategies.
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spelling pubmed-87080472021-12-25 Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection Lau, Chuen-Yen Adan, Matthew A. Maldarelli, Frank Viruses Review Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and that can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a reservoir of long-lived latently infected cells and their progeny. This proviral landscape undergoes change over time on ART. One of the forces driving change in the landscape is the clonal expansion of infected CD4 T cells, which presents a key obstacle to HIV eradication. Potential mechanisms of clonal expansion include general immune activation, antigenic stimulation, homeostatic proliferation, and provirus-driven clonal expansion, each of which likely contributes in varying, and largely unmeasured, amounts to maintaining the reservoir. The role of clinical events, such as infections or neoplasms, in driving these mechanisms remains uncertain, but characterizing these forces may shed light on approaches to effectively eradicate HIV. A limited number of individuals have been cured of HIV infection in the setting of bone marrow transplant; information from these and other studies may identify the means to eradicate or control the virus without ART. In this review, we describe the mechanisms of HIV-1 persistence and clonal expansion, along with the attempts to modify these factors as part of reservoir reduction and cure strategies. MDPI 2021-12-14 /pmc/articles/PMC8708047/ /pubmed/34960781 http://dx.doi.org/10.3390/v13122512 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lau, Chuen-Yen
Adan, Matthew A.
Maldarelli, Frank
Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title_full Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title_fullStr Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title_full_unstemmed Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title_short Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection
title_sort why the hiv reservoir never runs dry: clonal expansion and the characteristics of hiv-infected cells challenge strategies to cure and control hiv infection
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708047/
https://www.ncbi.nlm.nih.gov/pubmed/34960781
http://dx.doi.org/10.3390/v13122512
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