Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 with compartmentalized viral populations.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
05
12
2018
accepted:
24
05
2019
revised:
02
07
2019
pubmed:
21
6
2019
medline:
4
12
2019
entrez:
21
6
2019
Statut:
epublish
Résumé
We previously reported the presence of memory CD4+ T cells that express low levels of SAMHD1 (SAMHD1low) in peripheral blood and lymph nodes from both HIV-1 infected and uninfected individuals. These cells are enriched in Th17 and Tfh subsets, two populations known to be preferentially targeted by HIV-1. Here we investigated whether SAMHD1low CD4+ T-cells harbour replication-competent virus and compartimentalized HIV-1 genomes. We sorted memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-1-infected patients on anti-retroviral therapy (c-ART) and performed HIV-1 DNA quantification, ultra-deep-sequencing of partial env (C2/V3) sequences and phenotypic characterization of the cells. We show that SAMHD1low cells include novel Th17 CCR6+ subsets that lack CXCR3 and CCR4 (CCR6+DN). There is a decrease of the % of Th17 in SAMHD1low compartment in infected compared to uninfected individuals (41% vs 55%, p<0.05), whereas the % of CCR6+DN increases (7.95% vs 3.8%, p<0.05). Moreover, in HIV-1 infected patients, memory SAMHD1low cells harbour high levels of HIV-1 DNA compared to memory SAMHD1+ cells (4.5 vs 3.8 log/106cells, respectively, p<0.001), while naïve SAMHD1+ showed significantly lower levels (3.1 log/106cells, p<0.0001). Importantly, we show that SAMHD1low cells contain p24-producing cells. Moreover, phylogenetic analyses revealed well-segregated HIV-1 DNA populations with compartmentalization between SAMHD1low and SAMHD1+ memory cells, and limited viral exchange. As expected, the % of Ki67+ cells was significantly higher in SAMHD1low compared to SAMHD1+ cells. There was positive association between levels of HIV-1 DNA and Ki67+ in memory SAMHD1low cells, but not in memory and naïve SAMHD1+ CD4+ T-cells. Altogether, these data suggest that proliferative memory SAMHD1low cells contribute to viral persistence.
Identifiants
pubmed: 31220191
doi: 10.1371/journal.ppat.1007868
pii: PPATHOGENS-D-18-02327
pmc: PMC6605680
doi:
Substances chimiques
Anti-Retroviral Agents
0
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
SAMHD1 protein, human
EC 3.1.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007868Subventions
Organisme : NIAID NIH HHS
ID : R21 AI131971
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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