OVEREXPRESSION OF BASAL C-FOS AND C-JUN BUT NOT OF RAS ONCOGENES AFTER THEILERS MURINE ENCEPHALOMYELITIS VIRUS-INFECTION OF GLIAL-CELLS

Constitutive expression of the cellular proto-oncogenes c-fos and c-ju n, and in a lesser extent ras, was demonstrated in the glioma cell lin e C-6 by flow cytometry analysis using specific mono and polyclonal an tibodies. Basal expression of the products of the early response genes c-fos and c-jun were increased 66 and 50% when Theiler's murine encep halomyelitis virus (TMEV) infected these cells. No increase in ras tra nscription could be demonstrated after infection. This activation foll ows a kinetic reaching maximum values after 60 min and was proportiona l to the multiplicity of infection used. The described effect was comp letely abrogated by rabbit antibodies to TMEV but was not altered by n ormal rabbit serum. Furthermore, an intact infectious virion is needed to detect this effect. Fetal calf serum and lipopolysaccharide stimul ation slightly increases c-fos and c-jun expression following a slower kinetics. Cytokine treatment (IL-1 alpha, IL-6, IFN-gamma and TNF alp ha), did not induce oncogene over-expression. Therefore, this stimulat ion seems to be Linked to the TMEV infectious process.