Simian Immunodeficiency Virus and Antiretroviral Therapy Impact Rhesus Macaque Brain Lipid Distribution

Area of Science:

• Neuroscience
• Biochemistry
• Immunology

Background:

• Human immunodeficiency virus (HIV) infection causes significant brain strain, impacting energy balance and lipid homeostasis, even with antiretroviral therapy (ART).
• Brain lipid dysregulation in HIV/SIV infection is linked to increased energy demands, neuroinflammation, oxidative stress, and compromised blood-brain barrier integrity.
• Lipids are crucial in the brain, and their unique composition makes them susceptible to HIV-associated alterations.

Purpose of the Study:

• To investigate the spatial distribution and abundance of lipids in various brain regions and peripheral tissues of SIV-infected rhesus macaques receiving ART.
• To understand the impact of SIV infection and ART on phospholipid homeostasis across different anatomical locations.

Main Methods:

• Utilized mass spectrometry imaging (MSI) to analyze lipid profiles.
• Studied rhesus macaques experimentally infected with SIV and treated with a combination ART regimen (TDF, FTC, DTG).
• Compared lipid abundance and distribution across different brain regions (temporal cortex, hippocampus, midbrain) and peripheral tissues.

Main Results:

• Lipid abundance varied more significantly across different tissues than between treatment conditions.
• ART demonstrated a more pronounced effect on phospholipid homeostasis in the temporal cortex and hippocampus compared to the midbrain.
• ART administration robustly increased phospholipids in brain regions, whereas SIV infection had a variable impact dependent on the specific brain area.

Conclusions:

• ART significantly influences phospholipid levels in the brain, with regional differences possibly related to ART penetrance and turnover.
• SIV infection alters lipid profiles in a region-specific manner.
• Further research is needed to explore the neurological consequences of ART-driven lipid homeostasis changes in HIV-infected individuals.