Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS

Shaona Acharjee, Yu Zhu, Ferdinand Maingat, Carlos A Pardo-Villamizar, Klaus Ballanyi, Morley D. Hollenberg, Christopher Power

Research output: Contribution to journalArticle

Abstract

Distal sensory polyneuropathy is a frequent complication of lentivirus infections of the peripheral nervous system including both human immunodeficiency virus and feline immunodeficiency virus. Proteinase-activated receptors are G protein-coupled receptors implicated in the pathogenesis of neuroinflammation and neurodegeneration. Proteinase-activated receptor-1 is expressed on different cell types within the nervous system including neurons and glia, but little is known about its role in the pathogenesis of inflammatory peripheral nerve diseases, particularly lentivirus-related distal sensory polyneuropathy. Herein, the expression and functions of proteinase-activated receptor-1 in the peripheral nervous system during human immunodeficiency virus and feline immunodeficiency virus infections were investigated. Proteinase-activated receptor-1 expression was most evident in autopsied dorsal root ganglion neurons from subjects infected with human immunodeficiency virus, compared with the dorsal root ganglia of uninfected subjects. Human immunodeficiency virus or feline immunodeficiency virus infection of cultured human or feline dorsal root ganglia caused upregulation of interleukin-1β and proteinase-activated receptor-1 expression. In the human immunodeficiency virus-or feline immunodeficiency virus-infected dorsal root ganglia, interleukin-1β activation was principally detected in macrophages, while neurons showed induction of proteinase-activated receptor-1. Binding of proteinase-activated receptor-1 by the selective proteinase-activated receptor-1-activating peptide resulted in neurite retraction and soma atrophy in conjunction with cytosolic calcium activation in human dorsal root ganglion neurons. Interleukin-1β exposure to feline or human dorsal root ganglia caused upregulation of proteinase-activated receptor-1 in neurons. Exposure of feline immunodeficiency virus-infected dorsal root ganglia to the interleukin-1 receptor antagonist prevented proteinase-activated receptor-1 induction and neurite retraction. In vivo feline immunodeficiency virus infection was associated with increased proteinase-activated receptor-1 expression on neurons and interleukin-1β induction in macrophages. Moreover, feline immunodeficiency virus infection caused hyposensitivity to mechanical stimulation. These data indicated that activation and upregulation of proteinase-activated receptor-1 by interleukin-1β contributed to dorsal root ganglion neuronal damage during lentivirus infections leading to the development of distal sensory polyneuropathy and might also provide new targets for future therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)3209-3221
Number of pages13
JournalBrain
Volume134
Issue number11
DOIs
StatePublished - 2011

Fingerprint

PAR-1 Receptor
Spinal Ganglia
Feline Immunodeficiency Virus
Acquired Immunodeficiency Syndrome
HIV
Interleukin-1
Virus Diseases
Neurons
Polyneuropathies
Lentivirus Infections
Up-Regulation
Felidae
Peripheral Nervous System
Neurites
Macrophages
Proteinase-Activated Receptors
Lentivirus
Interleukin-1 Receptors
Carisoprodol
Peripheral Nervous System Diseases

Keywords

  • dorsal root ganglion
  • FIV
  • HIV
  • IL-1β

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Acharjee, S., Zhu, Y., Maingat, F., Pardo-Villamizar, C. A., Ballanyi, K., Hollenberg, M. D., & Power, C. (2011). Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS. Brain, 134(11), 3209-3221. https://doi.org/10.1093/brain/awr242

Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS. / Acharjee, Shaona; Zhu, Yu; Maingat, Ferdinand; Pardo-Villamizar, Carlos A; Ballanyi, Klaus; Hollenberg, Morley D.; Power, Christopher.

In: Brain, Vol. 134, No. 11, 2011, p. 3209-3221.

Research output: Contribution to journalArticle

Acharjee, S, Zhu, Y, Maingat, F, Pardo-Villamizar, CA, Ballanyi, K, Hollenberg, MD & Power, C 2011, 'Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS', Brain, vol. 134, no. 11, pp. 3209-3221. https://doi.org/10.1093/brain/awr242
Acharjee, Shaona ; Zhu, Yu ; Maingat, Ferdinand ; Pardo-Villamizar, Carlos A ; Ballanyi, Klaus ; Hollenberg, Morley D. ; Power, Christopher. / Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS. In: Brain. 2011 ; Vol. 134, No. 11. pp. 3209-3221.
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