Peripheral neuropathy in lentivirus infection: evidence of inflammation and axonal injury.
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-alpha 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).


CONCLUSIONS
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.
Kennedy
James M
JM
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
Hoke
Ahmet
A
Zhu
Yu
Y
Johnston
James B
JB
van Marle
Guido
G
Silva
Claudia
C
Zochodne
Douglas W
DW
Power
Christopher
C
D000818:Animals; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal; D002371:Cat Diseases / Q000276:immunology* / Q000473:pathology; D002415:Cats; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology; D016180:Lentivirus Infections / Q000276:immunology* / Q000473:pathology; D017969:Lentiviruses, Feline; D008262:Macrophage Activation; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000821:virology*; D012584:Sciatic Nerve / Q000276:immunology; D013497:Sural Nerve / Q000473:pathology