Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy

ADN del VIH-1; Cura del VIH-1; Reservorio de VIH-1

Detalles Bibliográficos
Autores: Gálvez, Cristina, Grau Exposito, Judit, Urrea, Victor, Clotet, Bonaventura, Falcó Ferrer, Vicenç, Buzón Gómez, María José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/7579
Acceso en línea:https://hdl.handle.net/11351/7579
http://hdl.handle.net/11351/7579
Access Level:acceso abierto
Palabra clave:Infeccions per VIH - Tractament
Antiretrovirals
DISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents
ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH
ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos
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oai_identifier_str oai:recercat.cat:11351/7579
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
title Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
spellingShingle Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
Gálvez, Cristina
Infeccions per VIH - Tractament
Antiretrovirals
DISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents
ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH
ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos
title_short Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
title_full Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
title_fullStr Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
title_full_unstemmed Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
title_sort Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
dc.creator.none.fl_str_mv Gálvez, Cristina
Grau Exposito, Judit
Urrea, Victor
Clotet, Bonaventura
Falcó Ferrer, Vicenç
Buzón Gómez, María José
author Gálvez, Cristina
author_facet Gálvez, Cristina
Grau Exposito, Judit
Urrea, Victor
Clotet, Bonaventura
Falcó Ferrer, Vicenç
Buzón Gómez, María José
author_role author
author2 Grau Exposito, Judit
Urrea, Victor
Clotet, Bonaventura
Falcó Ferrer, Vicenç
Buzón Gómez, María José
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Gálvez C, Urrea V] IrsiCaixa AIDS Research Institute, Badalona, Spain. [Grau-Expósito J, Falcó V, Buzón MJ] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Clotet B] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Fundació Lluita contra la SIDA, Badalona, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. [Martinez-Picado J] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Infeccions per VIH - Tractament
Antiretrovirals
DISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents
ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH
ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos
topic Infeccions per VIH - Tractament
Antiretrovirals
DISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents
ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH
ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos
description ADN del VIH-1; Cura del VIH-1; Reservorio de VIH-1
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/7579
http://hdl.handle.net/11351/7579
url https://hdl.handle.net/11351/7579
http://hdl.handle.net/11351/7579
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv mBio;12(6)
https://doi.org/10.1128/mBio.03078-21
info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0025%2F0007
info:eu-repo/grantAgreement/ES/PE2017-2020/RTI2018-101082-B-I00
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
image/tiff
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417461373206528
spelling Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral TherapyGálvez, CristinaGrau Exposito, JuditUrrea, VictorClotet, BonaventuraFalcó Ferrer, VicençBuzón Gómez, María JoséInfeccions per VIH - TractamentAntiretroviralsDISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV InfectionsOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV AgentsANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-LymphocytesENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIHOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIHANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivosADN del VIH-1; Cura del VIH-1; Reservorio de VIH-1HIV-1 DNA; HIV-1 cure; HIV-1 reservoirADN del VIH-1; Cura del VIH-1; Reservori del VIH-1Knowing the mechanisms that govern the persistence of infected CD4+ subpopulations could help us to design new therapies to cure HIV-1 infection. We evaluated the simultaneous distribution of the HIV-1 reservoir in 13 CD4+ subpopulations from 14 HIV-1-infected individuals on antiretroviral therapy to analyze its relationship with HIV-1 transcription, immune activation, and cell proliferation. A unique large blood donation was used to isolate CD4, CD4 resting (CD4r), CD4 activated (CD4a), T naive (TN), T stem cell memory (TSCM), T central memory (TCM), T transitional memory (TTM), T effector memory (TEM), circulating T follicular helper (cTFH), TCD20, TCD32, and resting memory TCD2high (rmTCD2high) cells. HIV-1 DNA measured by droplet digital PCR ranged from 3,636 copies/106 in TTM to 244 in peripheral blood mononuclear cells (PBMCs), with no subpopulation standing out for provirus enrichment. Importantly, all the subpopulations harbored intact provirus by intact provirus DNA assay (IPDA). TCD32, cTFH, and TTM had the highest levels of HIV-1 transcription measured by fluorescent in situ hybridization with flow cytometry (FISH/flow), but without reaching statistical differences. The subpopulations more enriched in provirus had a memory phenotype, were less activated (measured by CD38+/HLA-DR+), and expressed more programmed cell death 1 (PD-1). Conversely, subpopulations transcribing more HIV-1 RNA were not necessarily enriched in provirus and were more activated (measured by CD38+/HLA-DR+) and more proliferative (measured by Ki-67). In conclusion, the HIV reservoir is composed of a mosaic of subpopulations contributing to the HIV-1 persistence through different mechanisms such as susceptibility to infection, provirus intactness, or transcriptional status. The narrow range of reservoir differences between the different blood cell subsets tested suggests limited efficacy in targeting only specific cell subpopulations during HIV-1 cure strategies. IMPORTANCE The main barrier for HIV-1 cure is the presence of latently infected CD4+ T cells. Although various cell subpopulations have been identified as major HIV-1 reservoir cells, the relative contribution of infected CD4 subpopulations in the HIV-1 reservoir remains largely unknown. Here, we evaluated the simultaneous distribution of the HIV-1 reservoir in 13 CD4+ T-cell subpopulations in peripheral blood from HIV-1-infected individuals under suppressive antiretroviral therapy. We found that the HIV-1 reservoir is composed of a mosaic of cell subpopulations, with heterogeneous proviral DNA, HIV-1 transcription, and activation status. Hence, each cell subpopulation contributes to the HIV-1 persistence through different mechanisms such as susceptibility to infection, rates of intact provirus, transcriptional status or half-life. This research provides new insights into the composition of the HIV-1 reservoir, suggesting that, to be effective, eradication strategies must simultaneously target multiple cell subpopulations.This work was sponsored in part by Grifols and by Gilead (GLD17/00204). The funding organizations had no input in the design of the study or in the collection, analyses, and interpretation of the data. Similarly, they played no role in the writing of the manuscript or in the decision to submit the study for publication. J.M.-P. is supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation. J.M.-P. and M.J.B. are supported by the RETIC RD16/0025/0041 and RD16/0025/0007 (cofunded by the European Regional Development Fund/European Social Fund). M.J.B. is supported by grant RTI2018-101082-B-I00 (MINECO/FEDER) and by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). C.G. was supported by the Ph.D. fellowship of the Spanish Ministry of Education, Culture, and Sport (FPU15/03698).American Society for MicrobiologyInstitut Català de la Salut[Gálvez C, Urrea V] IrsiCaixa AIDS Research Institute, Badalona, Spain. [Grau-Expósito J, Falcó V, Buzón MJ] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Clotet B] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Fundació Lluita contra la SIDA, Badalona, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. [Martinez-Picado J] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfimage/tiffhttps://hdl.handle.net/11351/7579http://hdl.handle.net/11351/7579Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésmBio;12(6)https://doi.org/10.1128/mBio.03078-21info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0025%2F0007info:eu-repo/grantAgreement/ES/PE2017-2020/RTI2018-101082-B-I00Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/75792026-05-29T05:05:01Z
score 15,811543

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