Web of Science: 7 citas, Scopus: 8 citas, Google Scholar: citas,
Lack of concordance between residual viremia and viral variants driving de novo infection of CD4 + T cells on ART
Puertas, Maria C. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Noguera-Julian, Marc (Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), Vic, Spain)
Massanella, Marta (Département de Microbiologie, Infectiologie et Immunologie, Centre de Recherche du CHUM et Université de Montréal)
Pou, Christian (Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Stockholm Sweden)
Buzón, María José (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Clotet, Bonaventura (Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), Vic, Spain)
Stevenson, Mario (Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA)
Paredes, Roger (Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), Vic, Spain)
Blanco, Julià (Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), Vic, Spain)
Martinez-Picado, Javier (Institució Catalana de Recerca i Estudis Avançats (ICREA))

Fecha: 2016
Resumen: In most patients, current antiretroviral therapy (ART) regimens can rapidly reduce plasma viral load. However, even after years of effective treatment, a significant proportion of patients show residual plasma viremia below the clinical detection limit. Although residual viremia might be associated with increased chronic immune activation and morbidity, its origin and its potential role in the replenishment of the viral reservoir during suppressive ART is not completely understood. We performed an in-depth genetic analysis of the total and episomal cell-associated viral DNA (vDNA) repertoire in purified CD4 + T cell subsets of three HIV-infected individuals, and used phylogenetic analysis to explore its relationship with plasma viruses. The predominant proviral reservoir was established in naïve or memory (central and transitional) CD4 + T cell subsets in patients harboring X4- or R5-tropic viruses, respectively. Regardless of the viral tropism, most plasma viruses detected under suppressive ART resembled the proviral reservoir identified in effector and transitional memory CD4 + T-cell subsets in blood, suggesting that residual viremia originates from these cells in either blood or lymphoid tissue. Most importantly, sequences in episomal vDNA in CD4 + T-cells were not well represented in residual viremia. Viral tropism determines the differential distribution of viral reservoir among CD4 + T-cell subsets. In spite of viral tropism, the effector and transitional memory CD4 + T-cells subsets are the main source of residual viremia during suppressive ART, even though their contribution to the total proviral pool is small. However, the lack of concordance between residual viremia and viral variants driving de novo infection of CD4 + T cells on ART may reflect the predominance of defective plasma HIV RNA genomes. These findings highlight the need for monitoring the multiple viral RNA/DNA persistence markers, based on their differential contribution to viral persistence. The online version of this article (doi:10. 1186/s12977-016-0282-9) contains supplementary material, which is available to authorized users.
Nota: Número d'acord de subvenció MISPIIS#38035
Nota: Número d'acord de subvenció RD12/0017
Nota: Número d'acord de subvenció SAF2013‑49042‑R
Nota: Número d'acord de subvenció ISCIII/PI13/02014
Nota: Número d'acord de subvenció ISCIII/PI11/02098
Nota: Número d'acord de subvenció ISCIII/I14/01307
Nota: Altres ajuts: Gala Sida Barcelona 2010–14 i Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Materia: HIV-1 ; Viral reservoir ; Residual viremia ; Persistence ; CD4 + T cell subsets
Publicado en: Retrovirology, Vol. 13 (august 2016) , ISSN 1742-4690

PMID: 27484989
DOI: 10.1186/s12977-016-0282-9


15 p, 4.1 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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 Registro creado el 2018-02-07, última modificación el 2018-11-05



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