Adult Human Brain Tissue Cultures to Study NeuroHIV
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Recruitment
2.2. Collection of Brain Tissue, Blood, and Cerebrospinal Fluid
2.3. Human Brain Slice Culture
2.4. Tissue Clearing and Staining
2.5. Cell Culture
2.6. PBMC Isolation, CD4+ T-Cell Purification, and MDM Differentiation
2.7. Mechanical and Enzymatic Dissociation of Tissue Slices
2.8. Dendritic Spine Staining and Analysis
2.9. Multielectrode Array (MEA) Electrophysiology
2.10. Cloning and Plasmids
2.11. Preparation of Virus Stocks
2.12. Infection of Producer Cells and Inoculation of Tissue Slices
2.13. Quantification of Spreading Infection by p24 AlphaLISA
2.14. RNA Extraction, cDNA Synthesis, and qPCR from Tissue Slices
HIV-1 gag (0.8μM final): | 5′ GGTGCGAGAGCGTCAGTATTAAG 3′ |
5′ AGCTCCCTGCTTGCCCATA 3′ | |
GAPDH (0.4μM final): | 5′ GCTCACTGGCATGGCCTTCCGTGT 3′ |
5′ TGGAGGAGTGGGTGTCGCTGTTGA 3′ |
2.15. Flow Cytometry
2.16. Gating Strategy and Population Calculations
2.17. Experimental Design and Statistical Analysis
3. Results
3.1. Screening of Tissue Donors and Exclusion Criteria
3.2. Preparing Human Brain Organotypic Slice Cultures
3.3. Adult Human Brain Tissue Slices Are Viable Ex Vivo for at Least Four Weeks in Culture
3.4. Slice Cultures Maintain High Dendritic Spine Density with Mature Spine Morphologies
3.5. Multi-Electrode Array Recordings of Acute Brain Slices
3.6. Cell-Associated HIV-1 Infection of Ex Vivo Human Brain Slice Cultures
3.7. Human Brain Slices Inoculated with Infected MDMs and T-Cells Can Support an HIV-1 Spreading Infection Ex Vivo
3.8. Infected Brain Slice Cultures Contain Viral RNA and Can Be Suppressed by ARVs
3.9. HIV-1-Infected Slices Are Viable in Culture up to Nine Days Post-Infection
3.10. HIV-1-Infected, GFP+ Astrocytes and Myeloid Cells Are Present in Human Brain Tissue Inoculated with Infected MDMs and T-Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Age | N = 18 Cases |
Mean (SD) | 57.6 (14.2) |
Median | 58 |
Range | 33, 82 |
Sex, n (%) | |
Female | 11 (61.1) |
Male | 7 (38.9) |
Tissue collected, n (%) | |
Supratentorial neocortical parenchyma | 18 (100) |
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Van Duyne, R.; Irollo, E.; Lin, A.; Johnson, J.A.; Guillem, A.M.; O’Brien, E.V.; Merja, L.; Nash, B.; Jackson, J.G.; Sarkar, A.; et al. Adult Human Brain Tissue Cultures to Study NeuroHIV. Cells 2024, 13, 1127. https://doi.org/10.3390/cells13131127
Van Duyne R, Irollo E, Lin A, Johnson JA, Guillem AM, O’Brien EV, Merja L, Nash B, Jackson JG, Sarkar A, et al. Adult Human Brain Tissue Cultures to Study NeuroHIV. Cells. 2024; 13(13):1127. https://doi.org/10.3390/cells13131127
Chicago/Turabian StyleVan Duyne, Rachel, Elena Irollo, Angel Lin, James A. Johnson, Alain M. Guillem, Erick V. O’Brien, Laura Merja, Bradley Nash, Joshua G. Jackson, Atom Sarkar, and et al. 2024. "Adult Human Brain Tissue Cultures to Study NeuroHIV" Cells 13, no. 13: 1127. https://doi.org/10.3390/cells13131127
APA StyleVan Duyne, R., Irollo, E., Lin, A., Johnson, J. A., Guillem, A. M., O’Brien, E. V., Merja, L., Nash, B., Jackson, J. G., Sarkar, A., Klase, Z. A., & Meucci, O. (2024). Adult Human Brain Tissue Cultures to Study NeuroHIV. Cells, 13(13), 1127. https://doi.org/10.3390/cells13131127