Adenovirus-cell interactions early after infection: in vitro characteristics and tumourigenicity of adenovirus type 2-transformed rat liver epithelial cells

Abstract

Cloned rat liver epithelial cells (clone C3) were semi-permissive for adenovirus type 2 (Ad-2) and non-permissive for adenovirus type 12 (Ad-12). Ad-2-infected C3 cells were shown to produce hexon and fibre protein, but at an m.o.i. of 20 a maximum virus yield of only 2.4 p.f.u. per cell was obtained. Forty-eight h after infection with Ad-12 'early' virus proteins (major species 8K and 60K), but no 'late' proteins (virus structural proteins) could be identified. Of six Ad-2-transformed epithelial lines isolated from clone C3 only one was tumourigenic in syngeneic rats, whereas all six transformants produced tumours in athymic nude mice. There was a remarkable variation in the morphology of the Ad-2-transformed liver cells, ranging from an epithelial morphology similar to C3 cells to cells with a distinct lymphoid morphology. The in vitro and in vivo behaviour of the Ad-2-transformed clone C3 cells reported in this communication, taken together with our previous report on the characteristics of Ad-12-transformed C3 cells, clearly show that the differences observed between Ad-2- and Ad-12-transformed rat embryo cells were also observed in our studies using cloned rat liver epithelial cultures. Our findings clearly rule out the hypothesis that the heterogeneity of Ad-2-transformation events is the result of the transformation in vitro of different types of target cell.