Vaccinia growth factor stimulates cellular proliferation (hyperplasia) around infected cells. This effect is beneficial for virus replication in vivo, because poxviruses replicate possibly better in proliferating cells than in quiescent cells. Acts by binding host EGFR, inducing its dimerization, autophosphorylation and leading to activation of several cellular pathways regulating cell proliferation or cell survival. The activation by host EGFR of mitogen activated protein kinases (MAPK) and extracellular-signal regulated kinases (ERK) are essential for the positive effect of vaccinia growth factor on poxvirus virulence in vivo. Vaccinia growth factor interacts with host EGFR and promotes EGFR dimerization. Higher doses of VGF- virus than WT virus are required for intracranial lethality in mice and for production of skin lesions in rabbits. No effect in cell culture.