Bovine lactoferrin inhibits echovirus endocytic pathway by interacting with viral structural polypeptides.
Lactoferrin, an 80 kDa bi-globular iron-binding glycoprotein belonging to the transferrin family, is a pleiotropic factor with potent antimicrobial and immunomodulatory activities, present in breast milk, in mucosal secretions, and in the secondary granules of neutrophils. Recently, we have shown that bovine lactoferrin prevents the early phases of echovirus infection and also acts as a survival factor inhibiting viral-induced apoptosis. In the present research we investigated the mechanism of bovine lactoferrin anti-echoviral effect demonstrating that echovirus enters susceptible cells by an endocytic pathway and that lactoferrin treatment is able to prevent viral genome delivery into the cytoplasm. It is likely that lactoferrin interaction with echovirus capsid proteins induces alterations that stabilize the conformation of the virion making it resistant to uncoating. Taken together, the results of our study show that the inhibition of echovirus 6 infectivity by lactoferrin is dependent on its interaction not only with cell surface glycosaminoglycan chains but also with viral structural proteins demonstrating that this glycoprotein targets the virus entry process.