Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• HIV infection leads to persistent neurodegenerative effects on the central nervous system (CNS).
• These effects can continue even with effective antiretroviral therapy (ART).

Purpose of the Study:

• To map the transcriptomic and epigenetic landscapes of HIV-associated brain alterations.
• To explore region-specific and cross-regional changes in the CNS.
• To identify molecular shifts in brain cells that may cause ongoing neuroinflammation.

Main Methods:

• Single-nucleus multiome sequencing was performed on postmortem human brain samples.
• The study included samples from healthy individuals and individuals with a history of HIV and ART.
• Three brain regions were analyzed: prefrontal cortex, insular cortex, and ventral striatum.

Main Results:

• Widespread and persistent HIV-associated transcriptional and epigenetic alterations were found across multiple cell types.
• Microglia showed immune activation and metabolic dysregulation.
• Astrocytes exhibited distinct subpopulations, including a reactive type unique to HIV-infected brains.
• Cell-cell communication analyses revealed dysregulated, pro-inflammatory interactions among glial cells.

Conclusions:

• HIV infection induces distinct glial cell states with signatures of pro-inflammatory signaling and metabolic dysregulation.
• These persistent molecular changes in brain cells contribute to ongoing neuroinflammation and CNS dysfunction.
• The findings provide a framework for developing targeted therapies for HIV-associated neurological dysfunction.