Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Highly active antiretroviral therapy (HAART) has transformed HIV infection management.
• However, HIV-associated neurocognitive disorder (HAND) remains prevalent, affecting up to 50% of patients on HAART.
• The underlying mechanisms of HAND, particularly in the absence of active HIV encephalitis (HIVE), require further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying HAND.
• To identify gene expression patterns associated with HAND in patients on HAART.
• To explore the role of immune response pathways in HAND pathogenesis.

Main Methods:

• Gene co-expression network modular analysis was applied to gene expression profiles from the National NeuroAIDS Tissue Consortium (NNTC).
• Analysis focused on identifying dysregulated gene modules and associated regulatory factors.
• Immune response pathways and transcription factor regulation were specifically examined.

Main Results:

• A significant negative enrichment was observed for genes involved in immune response control.
• These downregulated immune genes are potentially regulated by transcription factors IRF8 and SPI1.
• Evidence suggests altered immune responses, mediated by type I and II interferons, are implicated in HAND.
• These immune alterations were detected even in cases without detectable HIV encephalitis (HIVE).

Conclusions:

• Altered immune responses play a critical role in the development of HAND.
• Dysregulation of specific immune pathways and transcription factors contributes to HAND pathogenesis.
• These findings highlight potential therapeutic targets for managing HAND, independent of active viral replication in the brain.