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Three-Dimensional Human Brain Organoids to Model HIV-1 Neuropathogenesis

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Virus-Host Interactions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2610))

Abstract

Studying neurological diseases have long been hampered by the lack of physiologically relevant models to resemble the complex human brain and the associated pathologies. Three-dimensional brain organoids have emerged as cutting-edge technology providing an alternative in vitro model to study healthy neural development and function as well as pathogenesis of neurological disorders and neuropathologies induced by pathogens. Nonetheless,  the absence of immune cells in current models poses a barrier to fully recapitulate brain microenvironment during the onset of HIV-1-associated neuropathogenesis. To address this and to further the brain organoid technology, we have incorporated HIV-target microglia into brain organoids, generating a complex multicellular interaction, which mimics the HIV-1-infected brain environment. Here we describe the method to generate a brain organoid consisting on neurons, astrocytes, and microglia (with and without HIV infection) that recapitulate the HIV-associated neuropathology. This model has tremendous potential to expand our knowledge on neuronal dysfunction associated with HIV-1 infection of glia.

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Acknowledgments

We thank Dr. Gengiz Geula from the Laboratory for Cognitive and Molecular Morphometry at Nothwestern University for donating the adult brain primary microglia cells for our study. This work is partially supported by the NIH (R37CA232209) and the start-up funds from Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh to Dr. Shilpa Sant.

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Authors and Affiliations

  1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Roberta S. dos Reis & Velpandi Ayyavoo

  2. Department of Pharmaceutical Sciences, School of Pharmacy, McGowan Institute for Regenerative Medicine, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Shilpa Sant

  3. Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA

    Shilpa Sant

  4. Departament of Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Roberta S. dos Reis

Authors
  1. Roberta S. dos Reis
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  2. Shilpa Sant
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  3. Velpandi Ayyavoo
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Corresponding author

Correspondence to Velpandi Ayyavoo .

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Editors and Affiliations

  1. Center for Radiological Research, Columbia University Irving Medical Cente, New York, NY, USA

    Marilena Aquino de Muro

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dos Reis, R.S., Sant, S., Ayyavoo, V. (2023). Three-Dimensional Human Brain Organoids to Model HIV-1 Neuropathogenesis. In: Aquino de Muro, M. (eds) Virus-Host Interactions. Methods in Molecular Biology, vol 2610. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2895-9_14

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  • DOI: https://doi.org/10.1007/978-1-0716-2895-9_14

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2894-2

  • Online ISBN: 978-1-0716-2895-9

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