Modeling HIV-1 Infection in CNS via Infected Monocytes Using Immunocompetent Brain Organoids

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• 3D brain organoid models offer advanced in vitro platforms for disease research.
• Human brain cytoarchitecture in HIV-1 neuropathogenesis can be recapitulated in brain organoids.
• Infected monocytes, macrophages, and microglia are key to HIV-1 dissemination and CNS latency in people with HIV (PWH).

Purpose of the Study:

• To develop an accessible protocol for incorporating monocytes into brain organoids.
• To model HIV-1 neuroinvasion and virus dissemination within the central nervous system (CNS).
• To enhance understanding of HIV-1 entry and latency establishment in the CNS for cure development.

Main Methods:

• Development of a 3D brain organoid model.
• Incorporation of infected and/or labeled peripheral monocytes into the organoid system.
• Utilizing the model to characterize HIV-1 transmigration, neuroinvasion, and dissemination.

Main Results:

• The brain organoid model successfully recapitulates key aspects of HIV-1 neuropathogenesis.
• The protocol allows for the study of monocyte transmigration into the brain organoid.
• The model facilitates the characterization of HIV-1 infection and spread within the CNS.

Conclusions:

• The developed brain organoid protocol provides a valuable tool for studying HIV-1 neuroinvasion.
• This model aids in understanding the mechanisms of HIV-1 latency in the CNS.
• Further research using this model can contribute to developing effective cure strategies for HIV-1.