HIV-1 TAT PROTEIN SUPPRESSES THE NERVE GROWTH-FACTOR (NGF)-MEDIATED DIFFERENTIATION OF PC12 RAT PHEOCHROMOCYTOMA CELL-LINE

In order to evaluate the effect of the regulatory human immunodeficien cy virus-type 1 (HIV-1) Tat protein on the process of neuronal differe ntiation, two tat-transfected and mock-transfected PC12 cell lines wer e cultured in the absence or presence of 100-1000 ng/ml of nerve growt h factor (NGF). As expected, NGF was able to induce a clearcut morphol ogical differentiation of mock-transfected PC12 into sympathetic-like neurons, also reducing the percentage of cells in S phase. On the othe r hand, NGF was unable to reduce the percentage of PC12-tat cells in S phase and/or to induce their neuronal differentiation. Only the addit ion in culture of 5 mu g/ml neutralizing anti-Tat antibody plus 1000 n g/ml NGF was effective in decreasing the percentage of PC12-tat in S p hase and inducing partial signs of neuronal differentiation in serum-f ree cultures. The ability of Tat protein to suppress the neuronal diff erentiation pathway controlled by NGF further contribute to the defini tion of its role in tumor promotion during the course of HTV-1 disease .