Combined single-cell transcriptional, translational, and genomic profiling reveals HIV-1 reservoir diversity.
Cell Rep
; 36(9): 109643, 2021 08 31.
Article
in En
| MEDLINE
| ID: mdl-34469719
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+) 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+ 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Protein Biosynthesis
/
RNA, Viral
/
Leukocytes, Mononuclear
/
HIV Infections
/
HIV-1
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Gene Expression Profiling
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Human Immunodeficiency Virus Proteins
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Single-Cell Analysis
/
Transcriptome
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article
Affiliation country: