Abstract
We demonstrate for the first time that the genome-wide profiling of HIV-infected peripheral blood mononuclear cells (PBMCs) from HIV-patients free of neurologic disease show overrepresentation of neurodegenerative pathways (Alzheimer’s, Parkinson’s, ALS, Huntington’s and Prion Disease, etc.) in genome-wide microarray analysis, which suggests that this genome-wide representation of neurodegenerative diseases-related pathways in PBMCs could possibly be a subcellular manifestation of neurologic interference by HIV. Further, the cell-tagging analysis attested this belief showing the large majority of genes tagged with cells of monocyte and macrophage lineage, which are implicated in neuronal dysfunction in both viral and non-viral neurodegenerative diseases. Together, these findings suggest that the genomic interference of HIV with neurodegenerative pathways is not by chance, but may be an early sign of HIV-mediated sub-genomic and sub-cellular manifestation of neurologic disease. Moreover, these findings signify the utility of PBMC and genome-wide mapping of the host gene expression as a powerful tool in predicting possible early events in neurologic deterioration in HIV patients.
Highlights
We demonstrate for the first time that the genome-wide profiling of HIV-infected peripheral blood mononuclear cells (PBMCs) from HIV-patients free of neurologic disease show overrepresentation of neurodegenerative pathways (Alzheimer’s, Parkinson’s, ALS, Huntington’s and Prion Disease, etc.) in genome-wide microarray analysis, which suggests that this genome-wide representation of neurodegenerative diseases-related pathways in PBMCs could possibly be a subcellular manifestation of neurologic interference by HIV
Neurological impairment is a common feature of Acquired Immunodeficiency Syndrome (AIDS) and other virus-mediated neurodegenerative diseases
Despite the success of highly active antiretroviral therapy (HAART) at reducing the incidence of HIV-associated neurocognitive disorders (HAND), there are still nearly 50% HIV-infected individuals who are predisposed to multiple cognitive domain deficits, such as psychomotor slowing, attention, memory, working memory, executive function, abstraction, verbal fluency, speed of information processing, sensory perceptual, and motor speed [1], which eventually will translate into HIV-associated dementia in >25% of HIV+ individuals on HAART
Summary
We demonstrate for the first time that the genome-wide profiling of HIV-infected peripheral blood mononuclear cells (PBMCs) from HIV-patients free of neurologic disease show overrepresentation of neurodegenerative pathways (Alzheimer’s, Parkinson’s, ALS, Huntington’s and Prion Disease, etc.) in genome-wide microarray analysis, which suggests that this genome-wide representation of neurodegenerative diseases-related pathways in PBMCs could possibly be a subcellular manifestation of neurologic interference by HIV. Peripheral blood mononuclear cells (PBMCs), which are involved in numerous immune related diseases, serve as highly valuable and informative surrogate material for gene expression studies. We have carried out a genome-wide profiling of the PBMCs from healthy controls and HIV-infected patients.
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