Induction of pathogenic sets of genes in macrophages and neurons in neuroAIDS

Eleanor S. Roberts, Michelle A. Zandonatti, Debbie D. Watry, Lisa J. Madden, Steven J. Henriksen, Michael A. Taffe, Howard S. Fox

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

The etiology of the central nervous system (CNS) alterations after human immunodeficiency virus (HIV) infection, such as dementia and encephalitis, remains unknown. We have used microarray analysis in a monkey model of neuroAIDS to identify 98 genes, many previously unrecognized in lentiviral CNS pathogenesis, whose expression is significantly upregulated in the frontal lobe of simian immunodeficiency virus-infected brains. Further, through immunohistochemical illumination, distinct classes of genes were found whose protein products localized to infiltrating macrophages, endothelial cells and resident glia, such as CD163, Glut5, and ISG15. In addition we found proteins induced in cortical neurons (ie, cyclin D3, tissue transglutaminase, α1-antichymotrypsin, and STAT1), which have not previously been described as participating in simian immunodeficiency virus or HIV-related CNS pathology. This molecular phenotyping in the infected brains revealed pathways promoting entry of macrophages into the brain and their subsequent detrimental effects on neurons. These data support the hypothesis that in HIV-induced CNS disease products of activated macrophages and astrocytes lead to CNS dysfunction by directly damaging neurons, as well as by induction of altered gene and protein expression profiles in neurons themselves which are deleterious to their function.

Original languageEnglish (US)
Pages (from-to)2041-2057
Number of pages17
JournalAmerican Journal of Pathology
Volume162
Issue number6
DOIs
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Roberts, E. S., Zandonatti, M. A., Watry, D. D., Madden, L. J., Henriksen, S. J., Taffe, M. A., & Fox, H. S. (2003). Induction of pathogenic sets of genes in macrophages and neurons in neuroAIDS. American Journal of Pathology, 162(6), 2041-2057. https://doi.org/10.1016/S0002-9440(10)64336-2