Glycosaminoglycans are not indispensable for the anti-herpes simplex virus type 2 activity of lactoferrin.
Lactoferrin has been recognized as a potent inhibitor of human herpetic viruses, such as herpes simplex type 1 (HSV-1) and 2 (HSV-2). In particular, bovine lactoferrin (bLf) has been found to prevent viral infection by binding to heparan sulphate (HS) glycosaminoglycans (GAGs) that in turn can act as cell receptors for human herpetic viruses. In this study we further investigate the mechanism of inhibiting activity of both human lactoferrin (hLf) and bLf against HSV-2. The antiviral effect of these proteins towards HSV-2 strain 333 and its glycoprotein C (gC)-truncated derivative HSV-2 gC-neg1 has been tested in monkey kidney cells. Our results indicate that the antiviral activity of bLf does not involve gC-HS interaction as there was no difference in its effectiveness towards wild type and mutant virus. As regards hLf, the mutant virus HSV-2 gC-neg1 was more sensitive compared to the wild type, suggesting that the human protein might interact with some viral structures that in wild-type viruses are masked by gC. When the modulation of HSV-2 infection by bLf and hLf was investigated under different experimental conditions, the bovine protein proved more effective than the human protein. Moreover, we found that, differently from what observed with HSV-1, bLf inhibited HSV-2 plaque-forming activity also in cells devoid of GAG expression. These results suggest that bLf may block a virus receptor of non-GAG nature and add new information on the anti-herpes virus activity of this protein, confirming it as an outstanding candidate for the treatment of herpetic infections.
Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. magda.marchetti@iss.it
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D000818:Animals; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D006025:Glycosaminoglycans / Q000494:pharmacology*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D051379:Mice
D006025:Glycosaminoglycans; D007781:Lactoferrin