Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques

ABSTRACT Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reserv...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Celina M. Abreu, Rebecca T. Veenhuis, Claudia R. Avalos, Shelby Graham, Daymond R. Parrilla, Edna A. Ferreira, Suzanne E. Queen, Erin N. Shirk, Brandon T. Bullock, Ming Li, Kelly A. Metcalf Pate, Sarah E. Beck, Lisa M. Mangus, Joseph L. Mankowski, Feilim Mac Gabhann, Shelby L. O’Connor, Lucio Gama, Janice E. Clements
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	HIV latency SIV macrophages monocytes Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bcbb18ba10ce487f8c86493a4d42ad7b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bcbb18ba10ce487f8c86493a4d42ad7b
record_format	dspace
spelling	oai:doaj.org-article:bcbb18ba10ce487f8c86493a4d42ad7b2021-11-15T16:22:10ZMyeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques10.1128/mBio.01659-192150-7511https://doaj.org/article/bcbb18ba10ce487f8c86493a4d42ad7b2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01659-19https://doaj.org/toc/2150-7511ABSTRACT Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir. We sought to determine whether tissue macrophages contribute to the SIVmac251 reservoir in suppressed macaques. Using cell-specific quantitative viral outgrowth assays (CD4-QVOA and MΦ-QVOA), we measured functional latent reservoirs in CD4s and macrophages in ART-suppressed SIVmac251-infected macaques. Spleen, lung, and brain in all suppressed animals contained latently infected macrophages, undetectable or low-level SIV RNA, and detectable SIV DNA. Silent viral genomes with potential for reactivation and viral spread were also identified in blood monocytes, although these cells might not be considered reservoirs due to their short life span. Additionally, virus produced in the MΦ-QVOA was capable of infecting healthy activated CD4s. Our results strongly suggest that functional latent reservoirs in CD4s and macrophages can contribute to viral rebound and reestablishment of productive infection after ART interruption. These findings should be considered in the design and implementation of future HIV cure strategies. IMPORTANCE This study provides further evidence that the latent reservoir is comprised of both CD4+ T cells and myeloid cells. The data presented here suggest that CD4+ T cells and macrophages found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. Additionally, we have shown that monocytes in blood contain latent virus and, though not considered a reservoir themselves due to their short life span, could contribute to the size of the latent reservoir upon entering the tissue and differentiating into long-lived macrophages. These new insights into the size and location of the SIV reservoir using a model that is heavily studied in the HIV field could have great implications for HIV-infected individuals and should be taken into consideration with the development of future HIV cure strategies.Celina M. AbreuRebecca T. VeenhuisClaudia R. AvalosShelby GrahamDaymond R. ParrillaEdna A. FerreiraSuzanne E. QueenErin N. ShirkBrandon T. BullockMing LiKelly A. Metcalf PateSarah E. BeckLisa M. MangusJoseph L. MankowskiFeilim Mac GabhannShelby L. O’ConnorLucio GamaJanice E. ClementsAmerican Society for MicrobiologyarticleHIVlatencySIVmacrophagesmonocytesMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV latency SIV macrophages monocytes Microbiology QR1-502
spellingShingle	HIV latency SIV macrophages monocytes Microbiology QR1-502 Celina M. Abreu Rebecca T. Veenhuis Claudia R. Avalos Shelby Graham Daymond R. Parrilla Edna A. Ferreira Suzanne E. Queen Erin N. Shirk Brandon T. Bullock Ming Li Kelly A. Metcalf Pate Sarah E. Beck Lisa M. Mangus Joseph L. Mankowski Feilim Mac Gabhann Shelby L. O’Connor Lucio Gama Janice E. Clements Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
description	ABSTRACT Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir. We sought to determine whether tissue macrophages contribute to the SIVmac251 reservoir in suppressed macaques. Using cell-specific quantitative viral outgrowth assays (CD4-QVOA and MΦ-QVOA), we measured functional latent reservoirs in CD4s and macrophages in ART-suppressed SIVmac251-infected macaques. Spleen, lung, and brain in all suppressed animals contained latently infected macrophages, undetectable or low-level SIV RNA, and detectable SIV DNA. Silent viral genomes with potential for reactivation and viral spread were also identified in blood monocytes, although these cells might not be considered reservoirs due to their short life span. Additionally, virus produced in the MΦ-QVOA was capable of infecting healthy activated CD4s. Our results strongly suggest that functional latent reservoirs in CD4s and macrophages can contribute to viral rebound and reestablishment of productive infection after ART interruption. These findings should be considered in the design and implementation of future HIV cure strategies. IMPORTANCE This study provides further evidence that the latent reservoir is comprised of both CD4+ T cells and myeloid cells. The data presented here suggest that CD4+ T cells and macrophages found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. Additionally, we have shown that monocytes in blood contain latent virus and, though not considered a reservoir themselves due to their short life span, could contribute to the size of the latent reservoir upon entering the tissue and differentiating into long-lived macrophages. These new insights into the size and location of the SIV reservoir using a model that is heavily studied in the HIV field could have great implications for HIV-infected individuals and should be taken into consideration with the development of future HIV cure strategies.
format	article
author	Celina M. Abreu Rebecca T. Veenhuis Claudia R. Avalos Shelby Graham Daymond R. Parrilla Edna A. Ferreira Suzanne E. Queen Erin N. Shirk Brandon T. Bullock Ming Li Kelly A. Metcalf Pate Sarah E. Beck Lisa M. Mangus Joseph L. Mankowski Feilim Mac Gabhann Shelby L. O’Connor Lucio Gama Janice E. Clements
author_facet	Celina M. Abreu Rebecca T. Veenhuis Claudia R. Avalos Shelby Graham Daymond R. Parrilla Edna A. Ferreira Suzanne E. Queen Erin N. Shirk Brandon T. Bullock Ming Li Kelly A. Metcalf Pate Sarah E. Beck Lisa M. Mangus Joseph L. Mankowski Feilim Mac Gabhann Shelby L. O’Connor Lucio Gama Janice E. Clements
author_sort	Celina M. Abreu
title	Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
title_short	Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
title_full	Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
title_fullStr	Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
title_full_unstemmed	Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
title_sort	myeloid and cd4 t cells comprise the latent reservoir in antiretroviral therapy-suppressed sivmac251-infected macaques
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/bcbb18ba10ce487f8c86493a4d42ad7b
work_keys_str_mv	AT celinamabreu myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT rebeccatveenhuis myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT claudiaravalos myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT shelbygraham myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT daymondrparrilla myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT ednaaferreira myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT suzanneequeen myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT erinnshirk myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT brandontbullock myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT mingli myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT kellyametcalfpate myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT sarahebeck myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT lisammangus myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT josephlmankowski myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT feilimmacgabhann myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT shelbyloconnor myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT luciogama myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques AT janiceeclements myeloidandcd4tcellscomprisethelatentreservoirinantiretroviraltherapysuppressedsivmac251infectedmacaques
_version_	1718426928381165568

Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques

Ejemplares similares