Peripheral neuropathy in lentivirus infection: Evidence of inflammation and axonal injury

James M. Kennedy, Ahmet Hoke, Yu Zhu, James B. Johnston, Guido Van Marle, Claudia Silva, Douglas W. Zochodne, Christopher Power

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: As distal sensory polyneuropathy (DSP) is a major neurological complication of HIV-1 infection, we investigated the extent of peripheral nervous system disease in animals infected with the lentivirus, feline immunodeficiency virus (FIV), because it causes neurological disease and immunosuppression in cats similar to HIV-1 in humans. Methods: After infection with a neurovirulent FIV molecular clone, neurobehavioral testing, nerve morphology, viral detection and load measurements were performed. Results: Neurobehavioral studies showed delayed withdrawal in response to a noxious stimulus among FIV-infected animals compared with sham-infected controls (P < 0.05). Dorsal root ganglia and sciatic nerves from FIV-infected ammals showed activated macrophages that were increased in number and size compared with controls. In addition, TNF-α messenger RNA was detectable in most nerves and spinal cords from the FIV-infected group, but was infrequently detected in controls. Viral RNA copy numbers in plasma and sciatic nerves were detectable in all FIV-infected animals at high levels. Studies of sural nerves identified myelinated fiber atrophy in 12-week FIV-infected animals compared with age-matched control animals, which was accompanied by reduced myelin sheath thickness (P < 0.05). The footpads of FIV-infected animals displayed reduced intraepidermal fiber density compared with control animals (P < 0.01). Conclusion: FIV infection results in the rapid onset of peripheral neuropathy, defined by axonal injury and macrophage activation, together with abundant virus within the nerve, indicating that it may serve as a model of HIV-related DSP.

Original languageEnglish (US)
Pages (from-to)1241-1250
Number of pages10
JournalAIDS
Volume18
Issue number9
DOIs
StatePublished - Jun 18 2004

Keywords

  • FIV
  • HIV-1
  • Inflammation
  • Lentivirus
  • Nerve morphometry
  • Neurobehavioral studies
  • Peripheral neuropathy
  • Viral load

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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