PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals.

Details

Serval ID
serval:BIB_FCD5348987A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals.
Journal
Nature medicine
Author(s)
Banga R., Procopio F.A., Noto A., Pollakis G., Cavassini M., Ohmiti K., Corpataux J.M., de Leval L., Pantaleo G., Perreau M.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
07/2016
Peer-reviewed
Oui
Volume
22
Number
7
Pages
754-761
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) serve as primary sites for HIV-1 replication. We sought to identify the memory CD4 T cell populations in blood and LNs that are responsible for the production of replication-competent and infectious HIV-1, as well as for active and persistent virus transcription in ART-treated (for 1.5-14.0 years), aviremic (<50 HIV RNA copies/ml) HIV-infected individuals. We demonstrate that LN CD4 T cells that express programmed cell death 1 (PDCD1; also known as PD-1), which are composed of about 65% T follicular helper cells as defined by the expression of the cell surface receptors CXCR5 and PD-1, are the major source of replication-competent HIV-1 and of infectious virus, as compared to any other (CXCR5(-)PD-1(-) and CXCR5(+)PD-1(-)) blood or LN memory CD4 T cell populations. LN PD-1(+) cells accounted for 46% and 96% of the total pools of memory CD4 T cells containing inducible replication-competent or infectious virus, respectively. Notably, higher levels of cell-associated HIV-1 RNA were present in LN PD-1(+) cells after long-term (up to 12 years) ART than in other memory CD4 T cell subpopulations. These results indicate that LN PD-1(+) cells are the major CD4 T cell compartment in the blood and LNs for the production of replication-competent and infectious HIV-1, and for active and persistent virus transcription in long-term-ART-treated aviremic individuals. Thus, these cells may represent a major obstacle to finding a functional cure for HIV-1 infection.

Keywords
Adult, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/metabolism, CD4-Positive T-Lymphocytes/virology, Case-Control Studies, Female, HIV Infections/drug therapy, HIV-1/genetics, HIV-1/physiology, Humans, Lymph Nodes/cytology, Lymph Nodes/virology, Male, Middle Aged, Programmed Cell Death 1 Receptor/metabolism, RNA, Viral/metabolism, Receptors, CXCR5/metabolism, T-Lymphocytes, Helper-Inducer/cytology, T-Lymphocytes, Helper-Inducer/metabolism, T-Lymphocytes, Helper-Inducer/virology, Virus Replication
Pubmed
Web of science
Create date
07/06/2016 8:35
Last modification date
20/08/2019 17:27
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