Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
30
07
2020
accepted:
04
12
2020
revised:
29
01
2021
pubmed:
20
1
2021
medline:
27
4
2021
entrez:
19
1
2021
Statut:
epublish
Résumé
The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.
Identifiants
pubmed: 33465157
doi: 10.1371/journal.ppat.1009214
pii: PPATHOGENS-D-20-01673
pmc: PMC7846027
doi:
Substances chimiques
Anti-Retroviral Agents
0
DNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009214Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007618
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI145806
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108349
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120387
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126611
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132128
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027757
Pays : United States
Organisme : NIAID NIH HHS
ID : K25 AI155224
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116368
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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