CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals

ABSTRACT The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains...

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Autores principales:	Xiaomin Li, Zhaoli Liu, Qijuan Li, Ronglin Hu, Lu Zhao, Yanyan Yang, Jiacong Zhao, Zhuoqiong Huang, Hongbo Gao, Linghua Li, Weiping Cai, Kai Deng
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	HIV-1 latent reservoir CD4+ T cells CD161 clonal expansion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9289ac1e47fe4017951770acb82031ff
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spelling	oai:doaj.org-article:9289ac1e47fe4017951770acb82031ff2021-11-15T15:59:41ZCD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals10.1128/mBio.02121-192150-7511https://doaj.org/article/9289ac1e47fe4017951770acb82031ff2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02121-19https://doaj.org/toc/2150-7511ABSTRACT The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4+ T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161+ CD4+ T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161+ CD4+ T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency. IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161+ CD4+ T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.Xiaomin LiZhaoli LiuQijuan LiRonglin HuLu ZhaoYanyan YangJiacong ZhaoZhuoqiong HuangHongbo GaoLinghua LiWeiping CaiKai DengAmerican Society for MicrobiologyarticleHIV-1latent reservoirCD4+ T cellsCD161clonal expansionHIV-1MicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 latent reservoir CD4+ T cells CD161 clonal expansion HIV-1 Microbiology QR1-502
spellingShingle	HIV-1 latent reservoir CD4+ T cells CD161 clonal expansion HIV-1 Microbiology QR1-502 Xiaomin Li Zhaoli Liu Qijuan Li Ronglin Hu Lu Zhao Yanyan Yang Jiacong Zhao Zhuoqiong Huang Hongbo Gao Linghua Li Weiping Cai Kai Deng CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
description	ABSTRACT The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4+ T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161+ CD4+ T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161+ CD4+ T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency. IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161+ CD4+ T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.
format	article
author	Xiaomin Li Zhaoli Liu Qijuan Li Ronglin Hu Lu Zhao Yanyan Yang Jiacong Zhao Zhuoqiong Huang Hongbo Gao Linghua Li Weiping Cai Kai Deng
author_facet	Xiaomin Li Zhaoli Liu Qijuan Li Ronglin Hu Lu Zhao Yanyan Yang Jiacong Zhao Zhuoqiong Huang Hongbo Gao Linghua Li Weiping Cai Kai Deng
author_sort	Xiaomin Li
title	CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
title_short	CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
title_full	CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
title_fullStr	CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
title_full_unstemmed	CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
title_sort	cd161<sup>+</sup> cd4<sup>+</sup> t cells harbor clonally expanded replication-competent hiv-1 in antiretroviral therapy-suppressed individuals
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9289ac1e47fe4017951770acb82031ff
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CD161<sup>+</sup> CD4<sup>+</sup> T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals

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