Vaccinia virus has two copies of a gene which has amino acid sequence homology with the receptor binding site of epidermal growth factor (EGF) and transforming growth factor (TGF-alpha). A 25 kilodalton glycoprotein (vaccinia virus growth factor (VGF) that can bind to EGF receptors) has been purified from media of virus infected BS-C-1 cells. When a mutant virus (VGF was constructed by removing both copies of the sequence encoding the putative EGF receptor binding site, the EGF receptor binding activity in infected cells was abolished. Inoculations of the VGF mutant into BALB/cBy) mice by the intracranial route and into the rabbit skin by the intradermal route resulted in reduced virus replication as compared to wild-type (WT) virus. No significant difference in plaguing efficiencies between WT and VGF mutant was observed in the presence of anti-EGF receptor antibody. This and other studies support the notion that VGF binding to the EGF receptor is not required for virus entry into host cells. Experiments both in vitro with resting cell lines and in vivo with the chicken embryo CAM suggest strongly that VGF acts on uninfected cells around the focus of infection inducing cellular proliferation, which increases the rate of virus replication and spread within the lesion and, presumably, the animal. Current studies are in progress to compare the ECG-like gene products from vaccinia virus with another poxvirus, Shope fibroma virus.
