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Adult Human Brain Tissue Cultures to Study NeuroHIV.

Rachel Van Duyne1, Elena Irollo1, Angel Lin1

  • 1Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.

Cells
|July 12, 2024
PubMed
Summary

A novel ex vivo human brain slice model allows researchers to study HIV-associated neurocognitive disorders (HAND) and test new therapeutics. This model maintains brain cell viability and function, enabling detailed investigation of HIV infection in the human brain.

Keywords:
HIV-1 infectionHIV-associated neurocognitive disorders (HAND)dendritic spine analysishuman brain organotypic slice culturesmicroelectrode array

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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Virology

Background:

  • HIV-associated neurocognitive disorders (HAND) remain a challenge despite antiretroviral therapy.
  • Existing cellular and animal models have limitations in fully recapitulating HAND pathology.
  • A need exists for human-centered models to study HAND mechanisms.

Purpose of the Study:

  • To develop and validate an ex vivo human brain slice model for studying HIV-1 infection.
  • To investigate the infection dynamics of HIV-1 in human brain tissue.
  • To provide a platform for testing neuroprotective therapeutics against HAND.

Main Methods:

  • Generated ex vivo human brain slice cultures from surgically resected tissue.
  • Assessed cell viability, neuronal morphology, and neuronal activity using flow cytometry and multi-electrode arrays.
  • Infected brain slices with HIV-1 using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs).
  • Quantified viral RNA expression and infection spread, and evaluated antiretroviral efficacy.

Main Results:

  • Brain slice cultures maintained high cell viability (>90%) and neuronal integrity for several weeks.
  • Infected slices showed viral RNA expression and spreading infection, which was reduced by antiretrovirals.
  • Infected myeloid cells and astrocytes were detected with minimal impact on overall cell viability.
  • The model demonstrated the potential to study HAND pathogenesis and therapeutic interventions.

Conclusions:

  • The ex vivo human brain slice model is a viable tool for studying HIV-1 infection in the human brain.
  • This model can elucidate cellular mechanisms underlying HAND, including antiretroviral toxicity and co-factors.
  • It serves as a promising platform for developing and testing novel neuroprotective strategies for HAND.