Gene expression patterns associated with neurological disease in HIV infection

Abstract

AbstractTo provide new insight into the pathogenesis of neurocognitive impairments (NCI) in HIV infection, we used the Gene Set Enrichment Analysis (GSEA) algorithm to analyze pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE). While HIVE was characterized by widespread inflammation and tissue damage, gene expression evidence of induction of interferon (IFN), cytokines and tissue injury was apparent in all brain regions studied before the emergence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. The latter showed a distinct pattern of immune activation with induction of chemokines, cytokines, β-defensins, and limited IFN induction.Altogether results indicate that significant neuroinflammation and neuronal suffering precede NCI. Patients with NCI without HIVE showed a predominantly white matter dysfunction with a distinct pattern of immune activation.