HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain

Shaona Acharjee, Farshid Noorbakhsh, Patrick L. Stemkowski, Camille Olechowski, Éric A. Cohen, Klaus Ballanyi, Bradley Kerr, Carlos A Pardo-Villamizar, Peter A. Smith, Christopher Power

Research output: Contribution to journalArticle

Abstract

Painful peripheral neuropathy has become the principal neurological disorder in HIV/AIDS patients. Herein, we investigated the effects of a cytotoxic HIV-1 accessory protein, viral protein R (Vpr), on the peripheral nervous system (PNS). Host and viral gene expression was investigated in peripheral nerves from HIV-infected individuals and in HIV-infected human dorsal root ganglion (DRG) cultures by RT-PCR and immunocytochemistry. Cytosolic calcium ([Ca2+]) fluxes and neuronal membrane responses were analyzed in cultured DRGs. Neurobehavioral responses and cytokine levels were assessed in a transgenic mouse model in which the vpr transgene was expressed in an immunodeficient background (vpr/RAG1-/-). Vpr transcripts and proteins were detected in peripheral nerves and DRGs from HIV-infected patients. Exposure of rat or human cultured DRG neurons to Vpr rapidly increased [Ca 2+] and action potential frequency while increasing input resistance. HIV infection of human DRG cultures caused neurite retraction (P-/- mice expressed Vpr together with increased IFN-α (P-/- littermates (P

Original languageEnglish (US)
Pages (from-to)4343-4353
Number of pages11
JournalFASEB Journal
Volume24
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Human Immunodeficiency Virus vpr Gene Products
vpr Gene Products
Nervous System Trauma
Peripheral Nervous System
Neurology
Neuralgia
HIV-1
Spinal Ganglia
HIV
Diagnosis-Related Groups
Peripheral Nerves
Viral Genes
Accessories
Peripheral Nervous System Diseases
Neurites
Nervous System Diseases
Transgenes
Gene expression
Transgenic Mice
Action Potentials

Keywords

  • Calcium imaging
  • Dorsal root ganglion
  • Electrophysiology
  • Interferon-α

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Acharjee, S., Noorbakhsh, F., Stemkowski, P. L., Olechowski, C., Cohen, É. A., Ballanyi, K., ... Power, C. (2010). HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. FASEB Journal, 24(11), 4343-4353. https://doi.org/10.1096/fj.10-162313

HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. / Acharjee, Shaona; Noorbakhsh, Farshid; Stemkowski, Patrick L.; Olechowski, Camille; Cohen, Éric A.; Ballanyi, Klaus; Kerr, Bradley; Pardo-Villamizar, Carlos A; Smith, Peter A.; Power, Christopher.

In: FASEB Journal, Vol. 24, No. 11, 11.2010, p. 4343-4353.

Research output: Contribution to journalArticle

Acharjee, S, Noorbakhsh, F, Stemkowski, PL, Olechowski, C, Cohen, ÉA, Ballanyi, K, Kerr, B, Pardo-Villamizar, CA, Smith, PA & Power, C 2010, 'HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain', FASEB Journal, vol. 24, no. 11, pp. 4343-4353. https://doi.org/10.1096/fj.10-162313
Acharjee S, Noorbakhsh F, Stemkowski PL, Olechowski C, Cohen ÉA, Ballanyi K et al. HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. FASEB Journal. 2010 Nov;24(11):4343-4353. https://doi.org/10.1096/fj.10-162313
Acharjee, Shaona ; Noorbakhsh, Farshid ; Stemkowski, Patrick L. ; Olechowski, Camille ; Cohen, Éric A. ; Ballanyi, Klaus ; Kerr, Bradley ; Pardo-Villamizar, Carlos A ; Smith, Peter A. ; Power, Christopher. / HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. In: FASEB Journal. 2010 ; Vol. 24, No. 11. pp. 4343-4353.
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