Vaccinia growth factor (VGF)

Vaccinia growth factor (VGF) is a viral protein produced by the Vaccinia virus that serves as a functional homolog of the human Epidermal Growth Factor (EGF). It is synthesized early during the viral life cycle and is secreted into the extracellular space after being cleaved by the host protease ADAM10 [1, 5]. VGF binds to the host's Epidermal Growth Factor Receptor (EGFR), triggering downstream signaling cascades such as the MAPK/ERK and mTORC1 pathways [2, 11]. These pathways promote the proliferation of neighboring uninfected cells and increase the motility of infected cells, both of which facilitate the rapid spread and efficient replication of the virus [1, 11]. In clinical applications, VGF is a primary target for genetic deletion in the development of oncolytic vaccinia viruses, such as Pexa-Vec, to enhance tumor selectivity and reduce virulence in healthy tissues [7, 16]. Inhibiting the VGF-EGFR axis with small molecule inhibitors like gefitinib or erlotinib is also explored as a strategy to limit poxvirus pathogenicity [12, 14]. Furthermore, VGF plays a role in reprogramming host metabolism, including the activation of the de novo pyrimidine synthesis pathway via the mTORC1-CAD axis [6, 8].

Other names

Pro-vaccinia growth factorOPG01919-kDa proteinVGF-like proteinVaccinia virus growth factor

Vaccinia growth factor acts as an agonist for the host Epidermal Growth Factor Receptor (EGFR), inducing receptor dimerization and activation of the MAPK/ERK and mTORC1 signaling pathways to promote host cell proliferation and viral dissemination [2, 11]. Therapeutic strategies include the use of EGFR inhibitors to block VGF-mediated signaling and the genetic deletion of VGF in oncolytic viruses to improve tumor selectivity [7, 14].