HIV in the cART era and the mitochondrial: immune interface in the CNS

Area of Science:

• Neuroscience
• Virology
• Cell Biology

Background:

• HIV-associated neurocognitive disorders (HAND) remain prevalent despite effective combined antiretroviral therapy (cART).
• Mitochondrial dysfunction is increasingly recognized as a key factor in the development of HAND during the cART era.
• The central nervous system (CNS) harbors HIV, leading to low-level viral protein expression that impacts mitochondrial health.

Purpose of the Study:

• To review evidence linking HIV proteins and cART drugs to mitochondrial dysfunction in the CNS.
• To explore the specific mechanisms of mitochondrial impairment in HAND.
• To summarize potential therapeutic strategies targeting mitochondrial dysfunction for HAND.

Main Methods:

• Review of human studies, animal models, and in vitro research.
• Analysis of evidence on HIV proteins (e.g., gp120, Tat, Vpr, Nef) and cART drugs affecting mitochondria.
• Examination of impacts on ATP production, mitochondrial dynamics, mitophagy, calcium signaling, apoptosis, oxidative stress, biogenesis, and immunometabolism.

Main Results:

• HIV proteins and cART drugs demonstrably induce mitochondrial dysfunction in the CNS.
• Specific alterations include impaired ATP synthesis, disrupted mitochondrial dynamics, altered mitophagy, and increased oxidative stress.
• Evidence extends to peripheral nervous system and other cell types, highlighting broad impact.

Conclusions:

• Mitochondrial dysfunction is a significant contributor to HAND pathogenesis.
• Therapeutic interventions targeting mitochondrial pathways hold promise for managing HAND.
• Further research into mitochondrial-based treatments is warranted to alleviate HAND symptoms.