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Combined single-cell transcriptional, translational, and genomic profiling reveals HIV-1 reservoir diversity.

Authors :
Sannier G
Dubé M
Dufour C
Richard C
Brassard N
Delgado GG
Pagliuzza A
Baxter AE
Niessl J
Brunet-Ratnasingham E
Charlebois R
Routy B
Routy JP
Fromentin R
Chomont N
Kaufmann DE
Source :
Cell reports [Cell Rep] 2021 Aug 31; Vol. 36 (9), pp. 109643.
Publication Year :
2021

Abstract

Although understanding the diversity of HIV-1 reservoirs is key to achieving a cure, their study at the single-cell level in primary samples remains challenging. We combine flow cytometric multiplexed fluorescent in situ RNA hybridization for different viral genes with HIV-1 p24 protein detection, cell phenotyping, and downstream near-full-length single-cell vDNA sequencing. Stimulation-induced viral RNA-positive (vRNA <superscript>+</superscript> ) cells from viremic and antiretroviral-therapy (ART)-suppressed individuals differ in their ability to produce p24. In participants on ART, latency-reversing agents (LRAs) induce a wide variety of viral gene transcription and translation patterns with LRA class-specific differences in reactivation potency. Reactivated proviruses, including in p24 <superscript>+</superscript> cells, are mostly defective. Although LRAs efficiently induce transcription in all memory cell subsets, we observe induction of translation mostly in effector memory cells, rather than in the long-lived central memory pool. We identify HIV-1 clones with diverse transcriptional and translational patterns between individual cells, and this finding suggests that cell-intrinsic factors influence reservoir persistence and heterogeneity.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
36
Issue :
9
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
34469719
Full Text :
https://doi.org/10.1016/j.celrep.2021.109643