Elevated Galectin-9 Across the Human Brain Correlates with HIV Neuropathology and Detrimental Cognitive States
JOURNAL OF NEUROVIROLOGY(2023)
摘要
HIV persistence and neuroinflammation are known to contribute to HIV-associated neuropathology. However, the multifaceted pathways driving impairment remain poorly understood. Galectin-glycan interactions have emerged as significant contributors to neuroinflammatory processes and may play a role in neuroHIV. Here, we quantified Galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, in post-mortem brain tissue across multiple regions from HIV-infected and HIV-uninfected donors to determine causal associations with HIV brain injury. We demonstrate that the staining intensity, total staining area, and cell-associated frequency of Gal-9 were elevated, principally in the frontal lobe and basal ganglia. Higher frontal lobe Gal-9 levels correlated with lower pre-mortem neuropsychological performance test scores in areas of attention and motor skills. Our results suggest that Gal-9 activity across the brain plays a role in neuroHIV pathogenesis and constitutes a promising disease-modifying target.
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关键词
NeuroHIV,Neuroinflammation,Cognition,Galectin
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