Single-cell analysis identifies cellular markers of the HIV permissive cell.

Details

Ressource 1Download: journal.ppat.1006678.pdf (4323.82 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_29071A53A66D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Single-cell analysis identifies cellular markers of the HIV permissive cell.
Journal
PLoS pathogens
Author(s)
Rato S., Rausell A., Muñoz M., Telenti A., Ciuffi A.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
10/2017
Peer-reviewed
Oui
Volume
13
Number
10
Pages
e1006678
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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".

Keywords
CD4-Positive T-Lymphocytes/immunology, Cells, Cultured, HIV Infections/immunology, HIV-1/immunology, Humans, Lymphocyte Activation/immunology, Single-Cell Analysis/methods, Virus Replication/physiology
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2017 20:01
Last modification date
20/08/2019 14:08
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