Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity.
Lactoferrin, a member of the transferrin family of approximately 80 kDa, consists of a single polypeptide chain folded in two symmetric, globular lobes (N- and C-lobes), each able to bind one ferric ion. This glycoprotein, found in physiological fluids of mammals, plays an important role in immune regulation and in defense mechanisms against bacteria, fungi, parasites, and viruses. Although the antiviral activity of lactoferrin is one of the major biological functions of such protein, the mechanism of action is still under debate. We have investigated both the role of tryptic fragments of bovine lactoferrin and the mechanism of lactoferrin antiviral effect toward adenovirus infection in HEp-2 cells. The results obtained demonstrated that the anti-adenovirus activity of lactoferrin is mediated by the N-terminal half of the protein as the N-lobe was able to inhibit adenovirus infection, even if at lower extent than undigested lactoferrin, whereas C-lobe was ineffective. The results also showed that the anti-adenovirus action of lactoferrin and of its N-terminal peptide lactoferricin took place on virus attachment to cell membrane, mainly through competition for common glycosaminoglycan receptors. The data provide evidence that the anti-adenovirus activity of lactoferrin is mediated mainly by the cluster of positive charges at the N-terminus of whole molecule and that the N-terminal peptide lactoferricin alone is sufficient to prevent infection.
Di Biase
Assunta Maria
AM
Laboratory of Ultrastructure, National Institute of Health, Rome, Italy.
Pietrantoni
Agostina
A
Tinari
Antonella
A
Siciliano
Rosa
R
Valenti
Piera
P
Antonini
Giovanni
G
Seganti
Lucilla
L
Superti
Fabiana
F
D000260:Adenoviruses, Human / Q000187:drug effects* / Q000472:pathogenicity; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D003588:Cytopathogenic Effect, Viral; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D010446:Peptide Fragments; D006493:Heparin; D007781:Lactoferrin