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Roadmap for spatial transcriptomics of HIV in tissues.

Qijie Guan1, Amare Eshetu, Ya-Chi Ho

  • 1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.

Current Opinion in HIV and AIDS
|July 8, 2025
PubMed
Summary

Spatial transcriptomic profiling reveals how HIV persists in tissues by examining infected cells and their environment. This technology offers new insights for developing targeted HIV therapies.

Keywords:
HIV cure strategiesHIV tissue reservoircell–cell interactionsimmune escapeimmune sanctuary sitelymph nodesingle-cell RNA-seqspatial multiomicsspatial transcriptomicstissue microenvironment

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genomics

Background:

  • HIV persistence in tissues differs from blood reservoirs.
  • Understanding tissue-level HIV reservoirs is crucial for eradication strategies.
  • Spatial transcriptomic profiling offers high-resolution insights into tissue microenvironments.

Purpose of the Study:

  • To provide an overview of spatial transcriptomic platforms for studying HIV persistence.
  • To detail a workflow for quality control and bioinformatic analysis of spatial transcriptomic data.
  • To highlight the utility of spatial profiling in understanding HIV-infected cell neighborhoods and interactions.

Main Methods:

  • Overview of various spatial transcriptomic platforms.
  • Workflow for data quality control, sanity checks, and bioinformatic analysis.
  • Discussion of factors influencing platform selection (resolution, coverage, RNA expression, tissue quality).

Main Results:

  • Advanced spatial transcriptomic profiling enables near-single cell resolution with genome-wide gene expression.
  • Poly-A-based mRNA capture can identify novel targets; targeted RNA capture enhances sensitivity in low-quality tissues.
  • Integration with ATAC-seq, protein capture, and TCR sequencing is an emerging area.

Conclusions:

  • Spatial transcriptomic profiling is key to uncovering HIV persistence mechanisms in tissues.
  • Findings can inform the development of novel therapeutic strategies against HIV.
  • Rigor in analysis, validation of findings, and biological significance are essential for interpretation.