Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection.
Adult
Aged
Antiviral Restriction Factors
CD4-Positive T-Lymphocytes
/ immunology
Carrier Proteins
/ genetics
Case-Control Studies
Cells, Cultured
Female
HIV Infections
/ immunology
HIV-2
/ genetics
Humans
Immunologic Memory
/ immunology
Leukocytes, Mononuclear
/ immunology
Male
Middle Aged
Receptors, CXCR6
/ genetics
Transcriptome
Tripartite Motif Proteins
Ubiquitin-Protein Ligases
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
15
11
2018
accepted:
10
04
2019
revised:
29
05
2019
pubmed:
17
5
2019
medline:
19
11
2019
entrez:
17
5
2019
Statut:
epublish
Résumé
The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models.
Identifiants
pubmed: 31095640
doi: 10.1371/journal.ppat.1007758
pii: PPATHOGENS-D-18-02196
pmc: PMC6541300
doi:
Substances chimiques
Antiviral Restriction Factors
0
CXCR6 protein, human
0
Carrier Proteins
0
Receptors, CXCR6
0
Tripartite Motif Proteins
0
TRIM5 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007758Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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