title: Involvement of bovine lactoferrin moieties in the inhibition of herpes simplex virus type 1 infection.
abstract: Bovine lactoferrin (BLf) is an iron binding protein folded in two lobes, N- and C-lobes. In this study we have reported the inhibitory activity towards herpes simplex virus type 1 (HSV-1) in vitro infection of BLf tryptic digested N- and C-lobes in comparison with the whole protein. The N-lobe and C-lobe exerted an anti-herpesvirus activity 50- and 10-fold lower than native BLf, respectively. In order to assess the phase of viral replication affected, lactoferrin-derived lobes were added to the cells at different non cytotoxic concentrations, during the whole cycle of viral infection or during viral attachment step, demonstrating that both lobes interfered with the early phases of infection. Among the BLf tryptic digested fragments, two negatively-charged small peptides deriving from N-lobe, previously shown effective towards HSV-1, have been further studied. We assessed that the net negative charge of these peptides was not responsible for the antiviral activity since their activity was not modified when the aspartic and glutamic acidic residues of these peptides were replaced with asparagine and glutamine, respectively. The experiments here reported confirm a pivotal role of N-lobe in inhibiting viral infection. However, the residual inhibiting activity of C-lobe and the similar efficacy shown by negatively or positively charged peptides strongly support the idea that the antiviral activity of bovine lactoferrin cannot be fully explained simply on the basis of competition between the protein and viral recognition sites for binding to glycosaminoglycans.
authors.affiliation: Microbiology Inst., University of Rome La Sapienza, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Seganti
authors.forename: A M
authors.initials: AM
authors.lastname: Di Biase
authors.forename: B
authors.initials: B
authors.lastname: Rega
authors.forename: B
authors.initials: B
authors.lastname: De Giulio
authors.forename: M
authors.initials: M
authors.lastname: Nicoletti
authors.forename: G
authors.initials: G
authors.lastname: Antonini
authors.forename: P
authors.initials: P
authors.lastname: Valenti