This paper describes the ability of human and bovine lactoferrins (HLf
; BLf), iron-binding proteins belonging to the non-immune defense syst
em, to interfere with herpes simplex virus type 1 (HSV-1) infection. S
ince lactoferrins are known to bind to heparan sulphate proteoglycans
and to low density lipoprotein receptor, which in turn act as binding
sites for the initial interaction of HSV-1 with host cells, we tested
the effect of these proteins on HSV-1 multiplication in Vero cells. Bo
th HLf and BLf are found to be potent inhibitors of HSV-1 infection, t
he concentrations required to inhibit the viral cytopathic effect in V
ero cells by 50% being 1.41 mu M and 0.12 mu M, respectively. HLf and
BLf exerted their activity through the inhibition of adsorption of vir
ions to the cells independently of their iron withholding property sho
wing similar activity in the apo- and iron-saturated form. The binding
of [S-35]methionine-labelled HSV-1 particles to Vero cells was strong
ly inhibited when BLf was added during the attachment step. BLf intera
cts with both Vero cell surfaces and HSV-1 particles, suggesting that
the hindrance of cellular receptors and/or of viral attachment protein
s may be involved in its antiviral mechanism.