TY - JOUR
T1 - Peripheral neuropathy in lentivirus infection
T2 - Evidence of inflammation and axonal injury
AU - Kennedy, James M.
AU - Hoke, Ahmet
AU - Zhu, Yu
AU - Johnston, James B.
AU - Van Marle, Guido
AU - Silva, Claudia
AU - Zochodne, Douglas W.
AU - Power, Christopher
PY - 2004/6/18
Y1 - 2004/6/18
N2 - 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.
AB - 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.
KW - FIV
KW - HIV-1
KW - Inflammation
KW - Lentivirus
KW - Nerve morphometry
KW - Neurobehavioral studies
KW - Peripheral neuropathy
KW - Viral load
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U2 - 10.1097/00002030-200406180-00002
DO - 10.1097/00002030-200406180-00002
M3 - Article
C2 - 15362656
AN - SCOPUS:3042685379
VL - 18
SP - 1241
EP - 1250
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 9
ER -