Human iPSC-derived brain organoids: A 3D mini-brain model for studying HIV infection

The brain is one of the important reservoir sites for HIV persistent/latent infection that often leads to HIV -associated neurocognitive disorders (HAND). However, HIV dynamics in the brain is an understudied area and little is known about mechanisms underlying the development and progression of HAND. This issue is mainly due to the lack of suitable in vitro models that can recapitulate the cellular and molecular complexity of the human brain. Hence, there is an urgent need for such models to study HIV neuropathogenesis and to develop therapeutics for HAND. The emergence of three-dimensional (3D) brain organoids generated from induced pluripotent stem cells (iPSCs) has now provided a clinically relevant in vitro model to study HIV brain infection and neuropathogenesis. Recently, there have been a noticeable number of publications that demonstrate the feasibility and advantages of this model for studies of neurobiology and brain disorders as well as HIV infection. Here, we describe the development of iPSC-derived human microglia-containing brain organoids, including advantages/challenges, and focus on their applicability for modeling HIV brain infection.

Automated summary

The brain is an important site for HIV infection, but little is known about the mechanisms underlying HIV-associated neurocognitive disorders due to a lack of suitable in vitro models. However, the development of three-dimensional brain organoids derived from induced pluripotent stem cells has provided a clinically relevant model for studying HIV infection in the brain. Recent publications have demonstrated the feasibility and advantages of this model for studying HIV neuropathology and developing therapeutics.