T cell-mediated SIV dissemination into the CNS: a single-cell transcriptomic analysis.
Xiaoke Xu1, Meng Niu1, Benjamin G Lamberty1
1University of Nebraska Medical Center.
Research Square
|May 19, 2025
Summary
CD4+ cytotoxic-like T cells initiate SIV entry into the brain, causing neuroinflammation. Brain myeloid cells may engulf these T cells, aiding viral spread in the central nervous system (CNS).
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Central nervous system (CNS) infection by HIV-1 causes neuroinflammation and cognitive issues.
- HIV-1 enters the brain via leukocytes like monocytes and CD4+ T cells.
- Cellular phenotypes enabling early CNS infection are not fully understood.
Purpose of the Study:
- Characterize brain lymphocyte roles during acute infection.
- Identify CD4+ T cell phenotypes that seed the CNS with SIV.
- Investigate interactions between infiltrating lymphocytes and brain myeloid cells.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) on brain and blood cells from SIV-infected macaques.
- Bioinformatic analysis of transcriptomic data.
- In vitro co-culture assays and re-analysis of public scRNA-seq data for validation.
Main Results:
- A brain cell cluster co-expressed myeloid and lymphoid genes, suggesting myeloid engulfment of CD4+ T cells.
- Proliferating CD4+ cytotoxic-like T cells increased, showing high viral entry receptor and adhesion molecule expression.
- Brain lymphocytes showed upregulated cytotoxic genes, MHC class II, ISG15, and USP18, indicating a strong immune response.
Conclusions:
- CD4+ cytotoxic-like T cells initiate SIV entry into the CNS, triggering neuroinflammation.
- Interactions between lymphocytes and brain myeloid cells may facilitate viral spread within the CNS.
