Gene expression for HIV-associated dementia and HIV encephalitis in microdissected neurons 1: preliminary analysis

Paul Shapshak^1,2, Robert Duncan³, E Margarita Duran⁴, Fabiana Farinetti⁵, Alireza Minagar⁶, Deborah Commins^7,8, Hector Rodriguez⁹, Francesco Chiappelli¹⁰, Pandajarasamme Kangueane^11,12, Andrew J Levine^8,13, Elyse Singer^8,13, Charurut Somboonwit^1,14, John T Sinnott^1,14
1Division of Infectious Disease and International Medicine, Tampa General Hospital, USF Health, Tampa, FL, USA; ²Department of Psychiatry and Behavioral Medicine, University of South Florida, College of Medicine, Tampa, FL, USA; ³Division of Biostatistics, Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL, USA; ⁴Viral Oncology Program, Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; ⁵Internal Medicine/Pediatrics, King's Daughter Medical Center, Ironton, OH, USA; ⁶Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; ⁷Department of Pathology, USC School of Medicine, Los Angeles, CA, USA; ⁸National Neurological AIDS Bank, UCLA School of Medicine, Westwood, CA, USA; ⁹Department of Biology, University of Miami, Coral Gables, FL, USA; ¹⁰Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA, USA; ¹¹Biomedical Informatics, Pondicherry, India; ¹²Asian Institute of Medicine, Science and Technology University, Bedong, Kedah, Malaysia; ¹³Department of Neurology, UCLA School of Medicine, Westwood, CA, USA; ¹⁴Clinical Research Unit, Hillsborough Health Department, Tampa, FL, USA

Abstract: We analyzed gene expression in neurons from 16 cases divided into four groups, ie, human immunodeficiency virus (HIV)-associated dementia (HAD)/HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV positive alone. We produced the neurons using laser capture microdissection from cryopreserved basal ganglia (specifically globus pallidus). Gene expression in pooled neurons from each case was analyzed on GE CodeLink Microarray chips with 55,000 gene fragments per chip. One-way analysis of variance showed significant changes in expression of 197 genes among the four groups (P < 0.005). The three groups, ie, HAD/HIVE, HAD alone, and HIVE alone, were compared with the HIV-positive group using Fisher's least significant difference test, and associated gene expression changes were assigned to each of the three comparisons. Identified genes were associated with 159 functional categories and many of the genes had more than one function. The functional groups included adhesion, amyloid, apoptosis, channel complex, cell cycle, chaperone, chromatin, cytokine, cytoskeleton, metabolism, mitochondria, multinetwork detection protein, sensory perception, receptor, ribosome, noncoding miRNA, signaling, synapse, transcription factor, homeobox, transport, multidrug resistance, and ubiquitin cycle. Several genes were associated with other neurodegenerative and developmental diseases, including Alzheimer's disease, Huntington's disease, and diGeorge syndrome. Thus, a wide range of dysregulated biochemical processes was reported in neuroanatomically precise neurons. This line of investigation is useful and provides specific information about gene expression dysfunction in NeuroAIDS.

Keywords: NeuroAIDS, human immunodeficiency virus, dementia, encephalitis, laser capture microdissection, globus pallidus, neuron, genes, expression