Tumor necrosis factor-alpha and virus expression in the central nervous system of cats infected with feline immunodeficiency virus

Cytokine disregulation has been implicated in the pathogenesis of lentiviru s-induced diseases. In the present study, 18 specific pathogen free (SPF) c ats were inoculated with feline immunodeficiency virus (FIV) Petaluma strai n and sacrificed at different times post-infection. Five additional SPF cat s were used as controls. The cell localization of the cytokine tumor necros is factor alpha (TNF-alpha) in the central nervous system (CNS) was determi ned by immunohistochemical and morphometric analyses with a polyclonal rabb it anti-human TNF-alpha antibody. TNF-alpha and FIV RNA were measured using competitive reverse transcriptase polymerase chain reaction (PCR) assays a nd the number of proviral genomes was estimated by competitive PCR. Portion s of frontal cortex were collected from each animal and both formalin-fixed and snap-frozen and stored at -80 degrees C until used. The results showed that TNF-alpha is present mainly in astrocytes and microglial cells. Morph ometric analysis showed that areas of TNF-alpha production increased in the early phases of infection. Molecular analyses demonstrated that the kineti cs of proviral loads in the CNS were comparable to what observed in lymph n odes and peripheral blood mononuclear cells, with the peaks in the early an d late stages of infection. A positive correlation was found between viral parameters and TNF-alpha transcription, the strongest relationship was foun d between the transcription of the cytokine and viral RNA load. These resul ts confirm that invasion of CNS by FIV occurs soon after virus exposure and that during this phase there is an increase of local viral loads with conc omitant up-regulation of TNF-alpha expression. During the asymptomatic phas e viral replication remains low in spite of the progression of CNS alterati ons. The dissociation between the viral load and the lesions observed sugge sts the importance of an indirect mechanism for the progression of these le sions, even if TNF-alpha seems to play a role particularly in the early pha se of infection.