Epidermal growth factor receptor occupancy inhibits vaccinia virus infection.
Vaccinia virus encodes VGF, an early protein of relative molecular mass 19,000 (19K) which, from amino-acid residues 45 to 85, is homologous in 19 residues to epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha). The conserved sequence includes a region of high homology (6 out of 10 amino acids) from residues 71 to 80, corresponding to the third disulphide loop of both EGF and TGF-alpha. This region has recently been shown to contain a binding region of TGF-alpha for the EGF receptor, and this raises the question of whether vaccinia virus utilizes the EGF receptor in order to bind to and infect cells. We now show that occupancy of the EGF receptor inhibits vaccinia virus infection. Inhibition is observed in a dose-dependent fashion by pre-treatment with either EGF or synthetic decapeptide antagonists of EGF's mitogenic activity which correspond to the sequence of the third disulphide loop of VGF or TGF-alpha. The relative ability of the peptides to inhibit vaccinia virus infection parallels their binding affinity to the EGF receptor.
D000818:Animals; D003588:Cytopathogenic Effect, Viral; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors; D005347:Fibroblasts; D051379:Mice; D008970:Molecular Weight; D010455:Peptides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015291:Transforming Growth Factors; D014616:Vaccinia virus / Q000472:pathogenicity*; D014779:Virus Replication
D010455:Peptides; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors