Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons

Sanjay C. Keswani, Michelle Polley, Carlos A Pardo-Villamizar, John W. Griffin, Justin Charles McArthur, Ahmet Hoke

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HIV-SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor-α and subsequent TNFR1-mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell-neuron interaction may be pathogenically relevant not only in HIV-SN but also in other peripheral neuropathies.

Original languageEnglish (US)
Pages (from-to)287-296
Number of pages10
JournalAnnals of Neurology
Volume54
Issue number3
DOIs
StatePublished - Sep 1 2003

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Chemokine Receptors
Schwann Cells
Sensory Receptor Cells
HIV-1
HIV
Receptors, Tumor Necrosis Factor, Type I
Neurons
Chemokine CCL5
Spinal Ganglia
Peripheral Nervous System Diseases
Viral Proteins
Virus Diseases
Peripheral Nerves
Cell Communication
Neuroglia
Ligation
Axons
Glycoproteins
Tumor Necrosis Factor-alpha
Apoptosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons. / Keswani, Sanjay C.; Polley, Michelle; Pardo-Villamizar, Carlos A; Griffin, John W.; McArthur, Justin Charles; Hoke, Ahmet.

In: Annals of Neurology, Vol. 54, No. 3, 01.09.2003, p. 287-296.

Research output: Contribution to journalArticle

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AU - Hoke, Ahmet

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AB - Human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HIV-SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor-α and subsequent TNFR1-mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell-neuron interaction may be pathogenically relevant not only in HIV-SN but also in other peripheral neuropathies.

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