serval:BIB_29071A53A66D
Single-cell analysis identifies cellular markers of the HIV permissive cell.
10.1371/journal.ppat.1006678
000414163300030
29073251
Rato
S.
author
Rausell
A.
author
Muñoz
M.
author
Telenti
A.
author
Ciuffi
A.
author
article
2017-10
PLoS pathogens
1553-7374
1553-7366
journal
13
10
e1006678
Cellular permissiveness to HIV infection is highly heterogeneous across individuals. Heterogeneity is also found across CD4+ T cells from the same individual, where only a fraction of cells gets infected. To explore the basis of permissiveness, we performed single-cell RNA-seq analysis of non-infected CD4+ T cells from high and low permissive individuals. Transcriptional heterogeneity translated in a continuum of cell states, driven by T-cell receptor-mediated cell activation and was strongly linked to permissiveness. Proteins expressed at the cell surface and displaying the highest correlation with T cell activation were tested as biomarkers of cellular permissiveness to HIV. FACS sorting using antibodies against several biomarkers of permissiveness led to an increase of HIV cellular infection rates. Top candidate biomarkers included CD25, a canonical activation marker. The combination of CD25 high expression with other candidate biomarkers led to the identification of CD298, CD63 and CD317 as the best biomarkers for permissiveness. CD25highCD298highCD63highCD317high cell population showed an enrichment of HIV-infection of up to 28 fold as compared to the unsorted cell population. The purified hyper-permissive cell subpopulation was characterized by a downregulation of interferon-induced genes and several known restriction factors. Single-cell RNA-seq analysis coupled with functional characterization of cell biomarkers provides signatures of the "HIV-permissive cell".
CD4-Positive T-Lymphocytes/immunology
Cells, Cultured
HIV Infections/immunology
HIV-1/immunology
Humans
Lymphocyte Activation/immunology
Single-Cell Analysis/methods
Virus Replication/physiology
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: epublish
University of Lausanne
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