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Vaccinia virus growth factor (VGF) is a secreted protein produced by poxviruses, such as the Vaccinia virus, that functions as a structural and functional homolog of the host epidermal growth factor (EGF) [2, 10]. VGF binds to and activates the host epidermal growth factor receptor (EGFR), triggering downstream signaling pathways including MAPK/ERK and PI3K/Akt that stimulate cell proliferation and increase cell motility in the vicinity of the infection [2, 3, 10]. This activation facilitates the rapid spread of the virus from cell to cell and contributes to the characteristic hyperplasia observed in poxvirus-infected tissues [2, 10]. Beyond its role in dissemination, VGF is critical for reprogramming host cell metabolism, specifically by upregulating the tricarboxylic acid (TCA) cycle and de novo pyrimidine biosynthesis to meet the high metabolic demands of viral replication [3, 6, 8]. Due to its role in virulence, VGF and its interaction with EGFR are significant therapeutic targets; host EGFR inhibitors like gefitinib and erlotinib have been investigated for their ability to limit viral spread [1, 3]. Additionally, VGF is a key factor in the design of oncolytic viruses, where its deletion is often used to enhance tumor selectivity and improve the safety profile of the viral vector [5, 6].
Competitive inhibition of the host epidermal growth factor receptor (EGFR) to block the signaling and proliferative effects induced by the viral growth factor.
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