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Gene Expression Profiles of HIV-1-Infected Glia and Brain: Toward Better Understanding of the Role of Astrocytes in HIV-1-Associated Neurocognitive Disorders

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Abstract

Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development, normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression. Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics to characterize the effects of HIV-1 and viral pathogenic proteins on cellular gene expression in astrocytes in vitro. We also present the first microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. In spite of different experimental conditions and microarray platforms used, comparison of the astrocyte array data sets reveals several common gene-regulatory changes that may underlie responses of these cells to HIV-1 and its proteins. We also compared the transcriptional profiles of astrocytes with those obtained in analyses of brain tissues of patients with HIV-1 dementia and macaques infected with simian immunodeficiency virus (SIV). Notably, many of the gene characteristics of responses to HIV-1 in cultured astrocytes were also altered in HIV-1 or SIV-infected brains. Functional genomics, in conjunction with other approaches, may help clarify the role of astrocytes in HIV-1 neuropathogenesis.

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Acknowledgments

The authors would like to thank Ms. Wannasiri Lapcharoensap for her help in experiments with mouse astrocytes, Dr. Mary Jane Potash for reviewing the manuscript, and Ms. Ilene M. Totillo for manuscript preparation. This work was supported by grants NS31492, DA017618, MH083627, and NS061646 from the National Institutes of Health, Public Health Service. The mouse astrocyte gene expression data described in this work are available in the NCBI Gene Expression Omnibus (GEO) database using accession number GSE17383.

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  1. Molecular Virology Division, St. Luke’s-Roosevelt Hospital Center, 432 West 58th Street, Antenucci Building, Room 709, New York, NY, 10019, USA

    Alejandra Borjabad, David J. Volsky & David J. Volsky

  2. Department of Pathology & Cell Biology, Columbia University, New York, NY, 10019, USA

    Alejandra Borjabad & David J. Volsky

  3. Environmental and Occupational Health Science Institute, Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA

    Andrew I. Brooks

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  1. Alejandra Borjabad
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Correspondence to David J. Volsky.

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Borjabad, A., Brooks, A.I. & Volsky, D.J. Gene Expression Profiles of HIV-1-Infected Glia and Brain: Toward Better Understanding of the Role of Astrocytes in HIV-1-Associated Neurocognitive Disorders. J Neuroimmune Pharmacol 5, 44–62 (2010). https://doi.org/10.1007/s11481-009-9167-1

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