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Review
. 2023 Sep 1;18(5):246-256.
doi: 10.1097/COH.0000000000000809. Epub 2023 Jul 17.

Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels

Michelle Wong  1 , Yulong Wei, Ya-Chi Ho
Affiliations
Review

Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels

Michelle Wong et al. Curr Opin HIV AIDS. .

Abstract

Purpose of review: The success of HIV-1 eradication strategies relies on in-depth understanding of HIV-1-infected cells. However, HIV-1-infected cells are extremely heterogeneous and rare. Single-cell multiomic approaches resolve the heterogeneity and rarity of HIV-1-infected cells.

Recent findings: Advancement in single-cell multiomic approaches enabled HIV-1 reservoir profiling across the epigenetic (ATAC-seq), transcriptional (RNA-seq), and protein levels (CITE-seq). Using HIV-1 RNA as a surrogate, ECCITE-seq identified enrichment of HIV-1-infected cells in clonally expanded cytotoxic CD4+ T cells. Using HIV-1 DNA PCR-activated microfluidic sorting, FIND-seq captured the bulk transcriptome of HIV-1 DNA+ cells. Using targeted HIV-1 DNA amplification, PheP-seq identified surface protein expression of intact versus defective HIV-1-infected cells. Using ATAC-seq to identify HIV-1 DNA, ASAP-seq captured transcription factor activity and surface protein expression of HIV-1 DNA+ cells. Combining HIV-1 mapping by ATAC-seq and HIV-1 RNA mapping by RNA-seq, DOGMA-seq captured the epigenetic, transcriptional, and surface protein expression of latent and transcriptionally active HIV-1-infected cells. To identify reproducible biological insights and authentic HIV-1-infected cells and avoid false-positive discovery of artifacts, we reviewed current practices of single-cell multiomic experimental design and bioinformatic analysis.

Summary: Single-cell multiomic approaches may identify innovative mechanisms of HIV-1 persistence, nominate therapeutic strategies, and accelerate discoveries.

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Conflict of interest statement

Conflicts of interest

None.

Figures

Figure 1.
Figure 1.
Single-cell multi-omics understanding of HIV-1 reservoir at the epigenetics, transcriptional, and protein level
See this image and copyright information in PMC

References

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      *The above two studies both measured the half-life of the HIV-1 latent reservoir to be around 44 months.

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