CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

Autores
Victoria, Sabina; Leyens, Johanna; Meckes, Lea Marie; Vavouras Syrigos, Georgios; Turk, Gabriela Julia Ana; Schindler, Michael
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
HIV-1 replication in macrophages is highly variable with internal virus accumulation in so-called virus-containing compartments (VCCs). VCCs represent a reservoir that is shielded from the antiviral immune response. VCC formation has been studied in lab-adapted HIV-1, but it has not been investigated whether primary HIV-1 strains induce VCCs. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, the effect of T cells on VCCs is unknown. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of non-infected CD4+ T cell coculture, and VCC formation. All HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated efficiently in macrophage monocultures. Coculture with non-infected CD4+ T cells enhanced the replication of primary HIV-1 in macrophages, a process associated with increased VCC formation and dependent on direct cell-to-cell contact. Broadly neutralizing antibodies differentially affectedaffectedaffectedCD4+ T cell-mediated enhancement of HIV-1 replication in macrophages. CD4 antibody treatment of macrophages phenocopied the infection-promoting effect of CD4+ T cell coculture. In conclusion, non-infected CD4+ T cells facilitate primary HIV-1 replication in macrophages, and the induction of VCCs appears to be a proxy for this phenotype. VCC formation and HIV-1 replication in macrophages are promoted by non-infected CD4+ T cells in a CD4- and GP120-dependent manner. Our findings highlight the critical role of T cell-macrophage interaction in HIV-1 replication dynamics and VCC formation and call for strategies to interfere with VCCs in order to target the HIV-1 reservoir in macrophages.
Fil: Victoria, Sabina. University Hospital Tübingen; Alemania
Fil: Leyens, Johanna. University Hospital Tübingen; Alemania
Fil: Meckes, Lea Marie. University Hospital Tübingen; Alemania
Fil: Vavouras Syrigos, Georgios. University Hospital Tübingen; Alemania
Fil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Schindler, Michael. University Hospital Tübingen; Alemania
Materia
HIV-1
MACROPHAGES
TRANSMITTED-FOUNDER
VIRUS-CONTAINING COMPARTMENTS
VCC
PRIMARY HIV-1 STRAINS
CELL-TO-CELL TRANSMISSION
VIRAL PERSISTENCE
VIRAL LATENCY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/280846
Acceder
id CONICETDig_0ba3f41f0b0696d82e0f1139c4d83f65
oai_identifier_str oai:ri.conicet.gov.ar:11336/280846
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartmentsVictoria, SabinaLeyens, JohannaMeckes, Lea MarieVavouras Syrigos, GeorgiosTurk, Gabriela Julia AnaSchindler, MichaelHIV-1MACROPHAGESTRANSMITTED-FOUNDERVIRUS-CONTAINING COMPARTMENTSVCCPRIMARY HIV-1 STRAINSCELL-TO-CELL TRANSMISSIONVIRAL PERSISTENCEVIRAL LATENCYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1HIV-1 replication in macrophages is highly variable with internal virus accumulation in so-called virus-containing compartments (VCCs). VCCs represent a reservoir that is shielded from the antiviral immune response. VCC formation has been studied in lab-adapted HIV-1, but it has not been investigated whether primary HIV-1 strains induce VCCs. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, the effect of T cells on VCCs is unknown. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of non-infected CD4+ T cell coculture, and VCC formation. All HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated efficiently in macrophage monocultures. Coculture with non-infected CD4+ T cells enhanced the replication of primary HIV-1 in macrophages, a process associated with increased VCC formation and dependent on direct cell-to-cell contact. Broadly neutralizing antibodies differentially affectedaffectedaffectedCD4+ T cell-mediated enhancement of HIV-1 replication in macrophages. CD4 antibody treatment of macrophages phenocopied the infection-promoting effect of CD4+ T cell coculture. In conclusion, non-infected CD4+ T cells facilitate primary HIV-1 replication in macrophages, and the induction of VCCs appears to be a proxy for this phenotype. VCC formation and HIV-1 replication in macrophages are promoted by non-infected CD4+ T cells in a CD4- and GP120-dependent manner. Our findings highlight the critical role of T cell-macrophage interaction in HIV-1 replication dynamics and VCC formation and call for strategies to interfere with VCCs in order to target the HIV-1 reservoir in macrophages.Fil: Victoria, Sabina. University Hospital Tübingen; AlemaniaFil: Leyens, Johanna. University Hospital Tübingen; AlemaniaFil: Meckes, Lea Marie. University Hospital Tübingen; AlemaniaFil: Vavouras Syrigos, Georgios. University Hospital Tübingen; AlemaniaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Schindler, Michael. University Hospital Tübingen; AlemaniaAmerican Society for Microbiology2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/280846Victoria, Sabina; Leyens, Johanna; Meckes, Lea Marie; Vavouras Syrigos, Georgios; Turk, Gabriela Julia Ana; et al.; CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments; American Society for Microbiology; Journal of Virology; 99; 4; 4-2025; 1-210022-538XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/jvi.00182-25info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.00182-25info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T12:10:27Zoai:ri.conicet.gov.ar:11336/280846instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-06 12:10:28.102CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
title CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
spellingShingle CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
Victoria, Sabina
HIV-1
MACROPHAGES
TRANSMITTED-FOUNDER
VIRUS-CONTAINING COMPARTMENTS
VCC
PRIMARY HIV-1 STRAINS
CELL-TO-CELL TRANSMISSION
VIRAL PERSISTENCE
VIRAL LATENCY
title_short CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
title_full CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
title_fullStr CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
title_full_unstemmed CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
title_sort CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments
dc.creator.none.fl_str_mv Victoria, Sabina
Leyens, Johanna
Meckes, Lea Marie
Vavouras Syrigos, Georgios
Turk, Gabriela Julia Ana
Schindler, Michael
author Victoria, Sabina
author_facet Victoria, Sabina
Leyens, Johanna
Meckes, Lea Marie
Vavouras Syrigos, Georgios
Turk, Gabriela Julia Ana
Schindler, Michael
author_role author
author2 Leyens, Johanna
Meckes, Lea Marie
Vavouras Syrigos, Georgios
Turk, Gabriela Julia Ana
Schindler, Michael
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HIV-1
MACROPHAGES
TRANSMITTED-FOUNDER
VIRUS-CONTAINING COMPARTMENTS
VCC
PRIMARY HIV-1 STRAINS
CELL-TO-CELL TRANSMISSION
VIRAL PERSISTENCE
VIRAL LATENCY
topic HIV-1
MACROPHAGES
TRANSMITTED-FOUNDER
VIRUS-CONTAINING COMPARTMENTS
VCC
PRIMARY HIV-1 STRAINS
CELL-TO-CELL TRANSMISSION
VIRAL PERSISTENCE
VIRAL LATENCY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv HIV-1 replication in macrophages is highly variable with internal virus accumulation in so-called virus-containing compartments (VCCs). VCCs represent a reservoir that is shielded from the antiviral immune response. VCC formation has been studied in lab-adapted HIV-1, but it has not been investigated whether primary HIV-1 strains induce VCCs. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, the effect of T cells on VCCs is unknown. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of non-infected CD4+ T cell coculture, and VCC formation. All HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated efficiently in macrophage monocultures. Coculture with non-infected CD4+ T cells enhanced the replication of primary HIV-1 in macrophages, a process associated with increased VCC formation and dependent on direct cell-to-cell contact. Broadly neutralizing antibodies differentially affectedaffectedaffectedCD4+ T cell-mediated enhancement of HIV-1 replication in macrophages. CD4 antibody treatment of macrophages phenocopied the infection-promoting effect of CD4+ T cell coculture. In conclusion, non-infected CD4+ T cells facilitate primary HIV-1 replication in macrophages, and the induction of VCCs appears to be a proxy for this phenotype. VCC formation and HIV-1 replication in macrophages are promoted by non-infected CD4+ T cells in a CD4- and GP120-dependent manner. Our findings highlight the critical role of T cell-macrophage interaction in HIV-1 replication dynamics and VCC formation and call for strategies to interfere with VCCs in order to target the HIV-1 reservoir in macrophages.
Fil: Victoria, Sabina. University Hospital Tübingen; Alemania
Fil: Leyens, Johanna. University Hospital Tübingen; Alemania
Fil: Meckes, Lea Marie. University Hospital Tübingen; Alemania
Fil: Vavouras Syrigos, Georgios. University Hospital Tübingen; Alemania
Fil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Schindler, Michael. University Hospital Tübingen; Alemania
description HIV-1 replication in macrophages is highly variable with internal virus accumulation in so-called virus-containing compartments (VCCs). VCCs represent a reservoir that is shielded from the antiviral immune response. VCC formation has been studied in lab-adapted HIV-1, but it has not been investigated whether primary HIV-1 strains induce VCCs. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, the effect of T cells on VCCs is unknown. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of non-infected CD4+ T cell coculture, and VCC formation. All HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated efficiently in macrophage monocultures. Coculture with non-infected CD4+ T cells enhanced the replication of primary HIV-1 in macrophages, a process associated with increased VCC formation and dependent on direct cell-to-cell contact. Broadly neutralizing antibodies differentially affectedaffectedaffectedCD4+ T cell-mediated enhancement of HIV-1 replication in macrophages. CD4 antibody treatment of macrophages phenocopied the infection-promoting effect of CD4+ T cell coculture. In conclusion, non-infected CD4+ T cells facilitate primary HIV-1 replication in macrophages, and the induction of VCCs appears to be a proxy for this phenotype. VCC formation and HIV-1 replication in macrophages are promoted by non-infected CD4+ T cells in a CD4- and GP120-dependent manner. Our findings highlight the critical role of T cell-macrophage interaction in HIV-1 replication dynamics and VCC formation and call for strategies to interfere with VCCs in order to target the HIV-1 reservoir in macrophages.
publishDate 2025
dc.date.none.fl_str_mv 2025-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/280846
Victoria, Sabina; Leyens, Johanna; Meckes, Lea Marie; Vavouras Syrigos, Georgios; Turk, Gabriela Julia Ana; et al.; CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments; American Society for Microbiology; Journal of Virology; 99; 4; 4-2025; 1-21
0022-538X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/280846
identifier_str_mv Victoria, Sabina; Leyens, Johanna; Meckes, Lea Marie; Vavouras Syrigos, Georgios; Turk, Gabriela Julia Ana; et al.; CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments; American Society for Microbiology; Journal of Virology; 99; 4; 4-2025; 1-21
0022-538X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/jvi.00182-25
info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.00182-25
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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 reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.106097

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