AI Article Synopsis
- The study explores how HIV invades the central nervous system, particularly affecting the basal ganglia, leading to neuroinflammation through extracellular vesicles (EVs) and their miRNA contents.
- Researchers utilized a simian immunodeficiency virus (SIV) model in rhesus macaques to discover that basal ganglia produce EVs and that these are influenced by both SIV infection and the cannabinoid THC.
- Results showed significant changes in miRNA profiles within these EVs, suggesting they play a role in inflammation and immune regulation, and indicating potential implications for HIV neuropathogenesis and treatment strategies.
Article Abstract
Background: Early invasion of the central nervous system (CNS) by human immunodeficiency virus (HIV) (Gray et al. in Brain Pathol 6:1-15, 1996; An et al. in Ann Neurol 40:611-6172, 1996), results in neuroinflammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 32:5174-5185, 2018; Hu et al. in Cell Death Dis 3:e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 33:1843-1852, 2019; Mintzopoulos et al. in Magn Reson Med 81:2896-2904, 2019), whether BG produces EVs and the effect of HIV and/or the phytocannabinoid-delta-9-tetrahydrocannabinol (THC) on BG-EVs and HIV neuropathogenesis remain unknown.
Methods: We used the simian immunodeficiency virus (SIV) model of HIV and THC treatment in rhesus macaques (Molina et al. in AIDS Res Hum Retroviruses 27:585-592, 2011) to demonstrate for the first time that BG contains EVs (BG-EVs), and that BG-EVs cargo and function are modulated by SIV and THC. We also used primary astrocytes from the brains of wild type (WT) and CX3CR1 mice to investigate the significance of BG-EVs in CNS cells.
Results: Significant changes in BG-EV-associated miRNA specific to SIV infection and THC treatment were observed. BG-EVs from SIV-infected rhesus macaques (SIV EVs) contained 11 significantly downregulated miRNAs. Remarkably, intervention with THC led to significant upregulation of 37 miRNAs in BG-EVs (SIV-THC EVs). Most of these miRNAs are predicted to regulate pathways related to inflammation/immune regulation, TLR signaling, Neurotrophin TRK receptor signaling, and cell death/response. BG-EVs activated WT and CX3CR1 astrocytes and altered the expression of CD40, TNFα, MMP-2, and MMP-2 gene products in primary mouse astrocytes in an EV and CX3CR1 dependent manners.
Conclusions: Our findings reveal a role for BG-EVs as a vehicle with potential to disseminate HIV- and THC-induced changes within the CNS.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469539 | PMC |
| http://dx.doi.org/10.1186/s12974-022-02586-9 | DOI Listing |
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