The Journal of Neuroscience, November 21, 2007, 27(47):12844-12850; doi:10.1523/JNEUROSCI.4154-07.2007
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Neurobiology of Disease
Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes
Eliseo A. Eugenin and
Joan W. Berman
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York 10461
Correspondence should be addressed to Dr. Eliseo A. Eugenin, Department of Pathology, F727, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Email: eeugenin{at}aecom.yu.edu
Human immunodeficiency virus (HIV) entry into the CNS is an early event after infection, resulting in neurological dysfunction in a significant number of individuals. As people with acquired immunodeficiency syndrome (AIDS) live longer, the prevalence of cognitive impairment is increasing, despite antiretroviral therapy. The mechanisms that mediate CNS dysfunction are still not completely understood, and include inflammation, viral presence, and/or replication. In this report, we characterize a novel role of gap junctions in transmitting and thereby amplifying toxic signals originating from HIV-infected astrocytes that trigger cell death in uninfected astrocytes. HIV-infected astrocytes were resistant to apoptosis; however, uninfected astrocytes forming gap junctions with infected astrocytes were apoptotic. Gap junction blockers abolished apoptosis in uninfected astrocytes, supporting the role of these channels in amplifying cell death. Our findings describe a novel mechanism of toxicity within the brain, triggered by low numbers of HIV-infected astrocytes and amplified by gap junctions, contributing to the pathogenesis of NeuroAIDS.
Key words: neuroinflammation; NeuroAIDS; apoptosis; chemokines; CCL2/MCP-1; Connexin
Received June 27, 2007;
accepted Oct. 5, 2007.
Correspondence should be addressed to Dr. Eliseo A. Eugenin, Department of Pathology, F727, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Email: eeugenin{at}aecom.yu.edu
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E. A. Eugenin, S. Morgello, M. E. Klotman, A. Mosoian, P. A. Lento, J. W. Berman, and A. D. Schecter
Human Immunodeficiency Virus (HIV) Infects Human Arterial Smooth Muscle Cells in Vivo and in Vitro: Implications for the Pathogenesis of HIV-Mediated Vascular Disease
Am. J. Pathol.,
April 1, 2008;
172(4):
1100 - 1111.
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