Many poxviruses encode homologs of the cellular epidermal growth factor (EGF)/transforming growth factor a (TGFa) family of ligands. Like their cellular counterparts, the poxviral growth factors are expressed as secreted proteins that bind to members of the erbB family of cellular receptors and induce a mitogenic response in the target cells. The first discovered viral example, and prototypic member of this family, is the vaccinia growth factor (VGF), which is synthesized as a membrane precursor and then later processed by proteolytic cleavage to the mature secreted ligand. It is believed that poxviruses utilize these growth factors as paracrine stimulators of neighboring uninfected cells in viral lesions to facilitate subsequent rounds of virus replication and cell cell spread.