Neuropathogenic mechanisms of feline immunodeficiency virus infection
We examined virological, neuropathological, and neurochemical parameters of cats infected at 3 days and 2 months of age. Following intravenous infection of neonatal cats with 1000 tissue culture infectious doses-50% of the Maryland strain of FIV, plasma viral loads were 6,600 to 1,200,000 copies per ml. Plasma loads did not correlate with leukocyte proviral loads; latencies of auditory, visual, and sensory evoked potentials; or brain viral and proviral loads. Of 16 cats tested, viral RNA was undetectable in frontal cortex of 13 and of caudate nucleus 14. Brain proviral load was detected in all cats tested. Infected cats in this study did not develop clinical neurological signs or AIDS. Cerebral subcortical white matter volume was reduced in cats infected as neonates and killed 3 months post inoculation (MPI), but was normal 6 MPI. Caudate nucleus volume was reduced 19% in cats infected as juveniles and killed 6 and 24 MPI compared to 6 month old controls . Cerebral neocortical gray matter volume was decreased 14% in cats infected as juveniles and killed 24 MPI compared. Histopathological lesions of cats infected as juveniles and adults (6 months old at infection) consisted of minimal lymphocytic infiltrates. No neuronal loss was observed by either necrotic or apoptotic mechanisms using fluoro-jade and stereological techniques. Neurochemical analysis of the caudate nucleus of cats infected as neonates revealed increased dopamine content at 3 and 18 MPI . Tyrosine hydroxylase immunoreactivity was increased 6 and 18 MPI . Tyrosine hydroxylase enzyme activity was increased only at 3 MPI. In the caudate nucleus, glutamate transporter (GLT1) mRNA was decreased 3 MPI and Glutamate was decreased 6 MPI. In the frontal cortex, glutamine synthetase activity was decreased 3 and 6 MPI, but glutamine was elevated at 3 MPI. In summary, lack of correlation between viral load and electrodiagnostics suggests host responses to infection perpetuate functional disturbances. Neocortical atrophy without neuronal loss might be reversible. Neurochemical abnormalities indicate altered dopamine synthesis and turnover in the caudate nucleus during infection. Reductions in GLT1 mRNA glutamine synthetase activity suggest astrocytic injury occurs.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:feline immunodeficiency virus neuroaids proviral load viral evoked potential neuropathology stereology neurochemistry dopamine tyrosine hydroxylase glutamate glutamine synthetase glt1 transporter brain central nerv
Date of Publication:01/01/2004