Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Adult human brain tissue cultures to study neuroHIV

Version 1 : Received: 19 April 2024 / Approved: 19 April 2024 / Online: 19 April 2024 (04:59:12 CEST)

How to cite: 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.; Klase, Z.A.; Meucci, O. Adult human brain tissue cultures to study neuroHIV. Preprints 2024, 2024041300. https://doi.org/10.20944/preprints202404.1300.v1 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.; Klase, Z.A.; Meucci, O. Adult human brain tissue cultures to study neuroHIV. Preprints 2024, 2024041300. https://doi.org/10.20944/preprints202404.1300.v1

Abstract

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

Keywords

HIV-associated neurocognitive disorders (HAND); human brain organotypic slice cultures; HIV-1 infection; dendritic spine analysis; microelectrode array

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.