Progressive Encephalopathy Associated with CD4/CD8 Inversion in Adult FIV-Infected Cats

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Abstract
Experimental intravenous challenge of five adult cats with the feline immunodeficiency virus Maryland isolate (FIV-MD) was investigated for its ability to induce neurologic abnormalities associated with the onset of immunodeficiency. Five 8-month-old cats were inoculated with 1000 median tissue culture infective dose of FIV-MD isolate, with five age-matched cats serving as uninfected controls. All FIV-MD-infected cats tested positive for serum antiviral antibodies and plasma viral DNA as detected by polymerase chain reaction at 2, 4, 10, and 16 months postinfection (PI). At 10 and 16 months PI, there was a significant reduction in the CD4/CD8 lymphocyte ratio, with all cats having a CD4/CD8 ratio of 1 or less. Total protein electrophoretic analysis of cerebrospinal fluid demonstrated a significantly increased albumin quotient at 4 and 16 months PI, representing a disrupted blood-brain barrier (BBB). At 16 months PI, all cats demonstrated a preferential increase in frontal cortical slow-wave activity compared with control cats. Serial evaluation of brainstem auditory evoked potential recordings revealed a prolongation of the interpeak latencies times over the study time. At least one abnormality was found over time in visual and somatosensory evoked potential testing in three and four infected cats, respectively. Comparing lymphocyte subtype ratios with neurologic testing revealed that every FIV-MD-infected cat exhibited an abnormality in at least one neurologic functional test with a concurrent CD4/CD8 count ratio of 1 or less. Overall, this study demonstrated that FIV-MD infection in adult cats results in a delayed-onset, progressive encephalopathy that parallels the decline in the CD4/CD8 lymphocyte ratio. Compared with prior information from pediatric FIV-MD-infected cats, these results indicate that age of infection influences the onset and severity of disease and may be associated with CD4 cell depletion in FIV-MD-infected cats, as seen in HIV-1-infected humans.