Implications of HIV persistence and pathogenesis in microglia

Area of Science:

• Neuroimmunology
• Virology
• Infectious Diseases

Background:

• HIV infection affects the brain, establishing a viral reservoir.
• Microglia, the brain's immune cells, are key players in HIV neuropathogenesis.
• Understanding viral persistence in microglia is vital for HIV cure research.

Purpose of the Study:

• To review recent advances in HIV brain infection, focusing on microglial persistence and pathogenesis.
• To highlight microglial research informing therapeutic strategies for the brain viral reservoir.
• To discuss approaches for HIV cure that address the central nervous system.

Main Methods:

• Review of current literature on HIV infection of the brain and microglia.
• Analysis of findings on viral persistence, pathogenesis, and therapeutic targets.
• Synthesis of research on microglial phenotypes and their role in neurodegeneration.

Main Results:

• Microglia harbor intact, inducible HIV proviruses, persisting even during antiretroviral therapy (ART).
• HIV-infected and bystander microglia show pro-inflammatory and senescent changes, mimicking aging and driving neuropathogenesis.
• ART partially mitigates but does not eliminate these detrimental microglial effects.

Conclusions:

• Microglial HIV reservoirs are central to brain pathogenesis and neurodegeneration.
• Characterizing the latent microglial reservoir and monitoring neurodegeneration are essential for HIV treatment and cure.
• Therapeutic strategies must reduce viral transcription and protein expression in the brain reservoir to combat neuroinflammation.