Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: Potential role in neuropathogenesis

被引：0

作者：

Wang Z. ^{[1
]}

Trillo-Pazos G. ^{[1
]}

Kim S.-Y. ^{[1
]}

Canki M. ^{[1
,6
]}

Morgello S. ^{[2
]}

Sharer L.R. ^{[3
]}

Gelbard H.A. ^{[4
]}

Su Z.-Z. ^{[5
]}

Kang D.-C. ^{[5
]}

Brooks A.I. ^{[4
]}

Fisher P.B. ^{[5
]}

Volsky D.J. ^{[1
]}

机构：

[1] Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, NY 10019, 432 West 58th St., Antenucci Bldg.

[2] Department of Pathology, The Mount Sinai Medical Center, New York, NY

[3] Department of Pathology, University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ

[4] Aab Biomedical Institute, Univ. of Rochester Medical Center, Rochester, NY

[5] Department of Pathology, Herbert Irving Compreh. Cancer Ctr., Columbia University, New York, NY

[6] Center for Immunology/Microbial Dis., Albany Medical College, Albany, NY

来源：

Journal of NeuroVirology | 2004年 / 10卷 / Suppl 1期

关键词：

Astrocytes; Glutamate transport; HAP; HIV-1; Microarrays;

D O I：

10.1080/753312749

中图分类号：

学科分类号：

摘要：

Neurodegeneration and dementia caused by human immunodeficiency virus type 1 (HIV-1) infection of the brain are common complications of acquired immunodeficiency syndrome (AIDS). Introduction of highly active antiretroviral therapy (HAART) reduced the incidence of HIV-1-associated dementia, but so far had no effect on the high frequency of milder neurological disorders caused by HIV-1. This indicates that some neuropathogenic processes persist during limited HIV-1 replication in the central nervous system (CNS). The authors are evaluating the hypothesis that interaction of HIV-1 with astrocytes, which bind HIV-1 but support limited productive HIV-1 infection, may contribute to these processes by disrupting astrocyte functions that are important for neuronal activity or survival. Using laser-capture microdissection on brain tissue samples from HIV-1-infected individuals, we found that HIV-1 DNA can be detected in up to 1% of cortical and basal ganglia astrocytes, thus confirming HIV-1 infection in astrocytes from symptomatic patients. Using rapid subtraction hybridization, the authors cloned and identified 25 messenger RNAs in primary human fetal astrocytes either up-regulated or down-regulated by native HIV-1 infection or exposure to gp120 in vitro. Extending this approach to gene microarray analysis using Affymetrix U133A/B gene chips, the authors determined that HIV-1 alters globally and significantly the overall program of gene expression in astrocytes, including changes in transcripts coding for cytokines, G-coupled protein receptors, transcription factors, and others. Focusing on a specific astrocyte function relevant to neuropathogenesis, the authors showed that exposure of astrocytes to HIV-1 or gp120 in vitro impairs the ability of the cells to transport L-glutamate and the authors related this defect to transcriptional inhibition of the EAAT2 glutamate transporter gene. These findings define new pathways through which HIV-1 may contribute to neuropathogenesis under conditions of limited virus replication in the brain. © 2004 Journal of NeuroVirology.

引用

页码：25 / 32

页数：7

共 62 条

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