NEUROVIRULENCE IN FELINE IMMUNODEFICIENCY VIRUS-INFECTED NEONATAL CATS IS VIRAL STRAIN-SPECIFIC AND DEPENDENT ON SYSTEMIC IMMUNE SUPPRESSION

Feline immunodeficiency virus (FIV) is a lentivirus that causes immune suppression and neurological disease in cats. Among animal viruses, i ndividual viral strains have been shown to be neurovirulent, but the r ole of viral strain specificity among lentiviruses and its relationshi p to systemic immune suppression in the development of neurological di sease remains uncertain. To determine the extent to which different FI V strains caused neurological disease, FIV V1CSF and Petaluma were com pared in ex vivo assays and in vivo. Both viruses infected and replica ted in macrophage and mixed glial cell cultures at similar levels, but V1CSF induced significantly greater neuronal death than Petaluma in a neurotoxicity assay. V1CSF-infected animals showed significant neurod evelopmental delay compared to the Petaluma-infected and uninfected an imals. Magnetic resonance spectroscopy studies of frontal cortex revea led significantly reduced N-acetyl aspartate/creatine ratios in the V1 CSF group compared to the other groups. Cyclosporin A treatment of Pet aluma-infected animals caused neurodevelopmental delay and reduced N-a cetyl aspartate/creatine ratios in the brain. Reduced CD4(+) and CD8() cell counts were observed in the V1CSF-infected group compared to th e uninfected and Petaluma-infected groups. These findings suggest that neurodevelopmental delay and neuronal injury is FIV strain specific b ut that systemic immune suppression is also an important determinant o f FIV-induced neurovirulence.