OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders

Area of Science:

• Neurovirology
• Immunology
• Genetics

Background:

• HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (c-ART).
• Neuronal damage in HAND is linked to chronic inflammation and immune activation.
• Mammalian 2'-5'-oligoadenylate synthetase (OAS) genes, induced by interferon (IFN), play a role in antiviral defense via RNase L activation.

Purpose of the Study:

• To investigate OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE) and HIV-associated neurocognitive disorders (HAND/HAD).
• To assess OAS gene network alterations in the central nervous system (CNS) in relation to viral load and c-ART status.

Main Methods:

• Analysis of three NCBI microarray datasets.
• Examination of brain biopsies from macaques with SIVE and post-mortem human brain tissues from individuals with HAND/HAD/HIVE.
• Comparison of OAS gene expression in infected subjects (on/off c-ART) versus uninfected controls.

Main Results:

• Upregulation of all OAS genes was observed in both SIVE and HAND models.
• Significantly higher OAS expression correlated with high viral loads and persisted in c-ART subjects.
• Upregulated OAS expression was detected in multiple brain regions (basal ganglia, white matter, frontal cortex) of HIV-infected individuals.

Conclusions:

• OAS gene family expression is elevated in the CNS during SIVE and HAND, likely induced by IFN due to viral replication.
• Sustained OAS upregulation may contribute to persistent neuroinflammation and cognitive impairment, even in treated individuals.
• Targeting the OAS-IFN pathway could offer therapeutic strategies for managing HAND.