Vaccinia virus growth factor induces divergent signaling programs and biological outcomes from cellular epidermal growth factor.

Vaccinia virus growth factor (VGF) activates EGFR in primary human foreskin fibroblasts but induces distinct downstream phosphorylation and biased kinase activity compared with epidermal growth factor (EGF).

• Why it matters: EGFR signaling controls key cell behaviors, and viruses hijack it to replicate; it was unclear whether VGF mimics EGF fully or selectively rewires pathways for viral replication.
• What they did: The study used quantitative global phosphoproteomics, kinase activity inference, and motif enrichment to compare EGF versus VGF signaling in primary human foreskin fibroblasts, with transcriptomics as a complementary readout.
• The result: VGF is more effective than EGF at promoting VACV plaque formation, supporting VGF-biased EGFR signaling nodes linked to viral spread.