Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics

Area of Science:

• Neuroimmunology
• Virology
• Genomics

Background:

• Microglia and macrophages are key brain immune cells targeted by HIV and SIV.
• SIV infection in nonhuman primates can cause neurological dysfunction, similar to HIV-associated neurocognitive disorder (HAND).
• Understanding in vivo myeloid cell responses during CNS infection is crucial.

Purpose of the Study:

• To investigate how myeloid cells in the brain respond to SIV-induced encephalitis (SIVE) using single-cell multiomic sequencing.
• To identify changes in gene expression and chromatin accessibility in brain myeloid cells during SIVE.
• To uncover the roles of different brain myeloid phenotypes in SIVE.

Main Methods:

• Single-cell multiomic sequencing (gene expression and ATAC-seq) was performed on myeloid cells from SIV-infected and control rhesus macaques.
• Analysis focused on identifying changes in cell populations, gene regulation, and chromatin accessibility.

Main Results:

• SIVE significantly altered myeloid cell populations in the brain.
• Microglia-like cells in SIVE expressed chemoattractants, recruiting activated cells to infection sites.
• A unique microglia-like cell population showed divergent chromatin accessibility and RNA expression.
• Upstream gene regulators and their targets in brain myeloid cells shifted dramatically during SIVE.

Conclusions:

• SIVE induces significant changes in brain myeloid cell populations and their functions.
• Distinct microglia-like cell phenotypes emerge during SIVE, with altered gene regulation.
• This study provides insights into the transcriptome, gene regulatory events, and roles of brain myeloid cells in SIVE.