Gap junctions mediate human immunodeficiency virus-bystander killing in astrocytes

Eliseo A. Eugenin, Joan W. Berman

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12844-12850
Number of pages7
JournalJournal of Neuroscience
Volume27
Issue number47
DOIs
StatePublished - Nov 21 2007
Externally publishedYes

Fingerprint

Gap Junctions
Astrocytes
HIV
Cell Death
Apoptosis
Virus Internalization
Poisons
Acquired Immunodeficiency Syndrome
Inflammation
Brain
Infection

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Apoptosis
  • CCL2/MCP-1
  • Chemokines
  • Connexin
  • NeuroAIDS
  • Neuroinflammation

Cite this

Eugenin, Eliseo A. ; Berman, Joan W. / Gap junctions mediate human immunodeficiency virus-bystander killing in astrocytes. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 47. pp. 12844-12850.
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Gap junctions mediate human immunodeficiency virus-bystander killing in astrocytes. / Eugenin, Eliseo A.; Berman, Joan W.

In: Journal of Neuroscience, Vol. 27, No. 47, 21.11.2007, p. 12844-12850.

Research output: Contribution to journalArticle

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AU - Berman, Joan W.

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