American Journal of Pathology 162:2041-2057 June 2003

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, and Howard S. Fox

From the Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California

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 up-regulated 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, alpha1-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.

Sample Information:

*Sample IDs link to information in the NCBI Gene Expression Omnibus

 

 

	Animal	Frontal Lobe		Occipital Lobe (Visual Cortex)	Midbrain	Cerebellum
		Replicate* 1	Replicate* 2		Replicate* 1	Replicate* 1
Control	298	042601_HF_298FL	021301_HF_298FL		032801_HF_298MB	052401_HF_298CB
	331	052201_HF_331FL	051801_HF_331FL	051801_HF_331VC	070302_HF_331MB	052401_HF_331CB
	332	042601_HF_332_FL	021301_HF_332FL		032801_HF_332MB	052401_HF_332CB
	357	042601_HF_357FL	021301_HF_357FL		032801_HF_357MB	052401_HF_357CB
	392	080301_HF_392Fl	080201_HF_392Fl
	393	112101_HF_393FL	111601_HF_393FL	111601_HF_393VC		111601_HF_393CB
SIVE	289	013102_HF_289FL	020102_HF_289FL		070302_HF_289MB	071202_HF_289CB
	301	020602_HF_301FL	020502_HF_301FL	070302_HF_301VC	070302_HF_301MB	070302_HF_301CB
	321	021301_HF_321FL	042601_HF_321FL	041101_HF_321VC	032801_HF_321MB	052401_HF_321CB
	323	042601_HF_323FL	021301_HF_323	041101_HF_323VC		052401_HF_323CB
	328	020102_HF_328FL	013102_HF_328FL		071202_HF_328MB	070302_HF_328CB
	330	042601_HF_330FL	032801_HF_330FL	041101_HF_330VC
* Replicates represent technical replicates in which the same hybridization cocktail was applied to two arrays.