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Updated: May 5, 2026
Multicolor Flow Cytometry Analyses of Cellular Immune Response in Rhesus Macaques
Published on: April 22, 2010
Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics
Xiaoke Xu1, Meng Niu1, Benjamin G Lamberty1
1Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Abstract:
The primary immune constituents in the brain, microglia and macrophages, are the target for HIV in people and simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological dysfunction, known as HIV-associated neurocognitive disorder (HAND). Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we perform single-cell multiomic sequencing, including gene expression and ATAC-seq, on myeloid cells from the brains of rhesus macaques with SIV-induced encephalitis (SIVE) as well as uninfected controls. We find that SIVE significantly changes the myeloid cell populations. In SIVE, microglia-like cells express high levels of chemoattractants capable of recruiting highly activated CAM-like cells to the site of infection/inflammation. A unique population of microglia-like cells is found in which the chromatin accessibility of genes diverges from their RNA expression. Additionally, we observe a dramatic shift of upstream gene regulators and their targets in brain myeloid cells during SIVE. This study further uncovers the transcriptome, gene regulatory events, and potential roles of different brain myeloid phenotypes in SIVE. This might deepen the understanding of SIVE/HIVE and enlighten the therapeutic development.
Insights
Simian immunodeficiency virus (SIV) infection alters brain myeloid cells, including microglia. This study reveals unique cell states and gene regulation changes during SIV-induced encephalitis (SIVE), offering insights into neurological complications.
Area of Science:
- Neuroimmunology
- Virology
- Genomics
Background:
- Microglia and macrophages are key brain immune cells targeted by HIV and SIV.
- HIV-associated neurocognitive disorder (HAND) results from CNS infection, but in vivo cellular responses are poorly understood.
- Simian immunodeficiency virus-induced encephalitis (SIVE) in macaques models HAND.
Purpose of the Study:
- To investigate in vivo myeloid cell responses to SIV infection in the brain.
- To characterize changes in gene expression and chromatin accessibility in brain myeloid cells during SIVE.
- To uncover gene regulatory events and cellular phenotypes in SIVE.
Main Methods:
- Single-cell multiomic sequencing (gene expression and ATAC-seq) on myeloid cells from SIV-infected and control rhesus macaques.
- Analysis of cellular populations, gene regulation, and chromatin accessibility.
- Comparative analysis between SIVE and control groups.
Main Results:
- SIVE significantly alters brain myeloid cell populations.
- Microglia-like cells in SIVE express chemoattractants, recruiting activated CAM-like cells.
- A unique microglia-like cell population shows divergent chromatin accessibility and RNA expression.
- Significant shifts in upstream gene regulators and their targets were observed in myeloid cells during SIVE.
Conclusions:
- SIVE induces profound changes in brain myeloid cell populations and gene regulation.
- The findings reveal novel cellular phenotypes and regulatory mechanisms in SIVE.
- This research deepens the understanding of SIVE/HIVE pathogenesis and may inform therapeutic strategies.
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