Human lactoferrin but not lysozyme neutralizes HSV-I and inhibits HSV-I replication and cell-to-cell spread

Institute of Dentistry, University of Turku, Turku, Finland.
Virology Journal (Impact Factor: 2.18). 06/2009; 6(1):53. DOI: 10.1186/1743-422X-6-53
Source: PubMed


The frequent oral shedding of herpes simplex virus type 1 (HSV-1) in the absence of clinical disease suggests that symptomatic HSV-1 recurrences may be inhibited by the mucosal environment. Indeed, saliva has been shown to contain substances with anti-HSV activity. In the current study, we investigated the anti-HSV-1 activity of human lactoferrin (hLf) and lysozyme (hLz), two highly cationic polypeptides of the mucosal innate defence system.
HLf blocked HSV-1 infection at multiple steps of the viral replication cycle, whereas lysozyme displayed no anti-HSV-1 activity. Preincubation of HSV-1 virions and presence of hLf during or after viral absorption period or for the entire HSV-1 infection cycle inhibited HSV-1 infection by reducing both the plaque count and plaque size in a dose- and virus strain-dependent manner. Cell-to-cell spread of wild-type HSV-1 and the strain gC-39, deleted of glycoprotein C, was dramatically reduced, but the cell-to-cell spread of HSV-1 Rid1, harboring a mutated gD and thus unable to react with the cellular HVEM receptor, remained unchanged. This suggests that the inhibition of cell-to-cell spread is mediated by effects on gD or its cellular counterparts.
Our results show that the cationic nature is not a major determinant in the anti-HSV action of mucosal innate cationic polypeptides, since whereas hLf inhibited HSV-1 infection efficiently, hLz had no HSV-1 inhibiting activity. Our results show that in addition to inhibiting the adsorption and post-attachment events of HSV-1 infection, hLf is also able to neutralize HSV-1 and that the inhibition of cell-to-cell spread involves viral gD. These results suggest that Lf may have a significant role in the modulation of HSV-1 infection in the oral cavity as well as in the genital mucosa, the major sites of HSV-1 infection.

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    • "Lactoferrin also binds bacterial fimbrial adhesins, and therefore inhibit epithelial adhesion of certain bacteria [26]. Antiviral activity of lactoferrin [76] is expected to be based on binding (and blocking) of certain host cell glycosaminoglycans used by viruses for adsorption [63]. Lactoferrin may also neutralize viruses by direct binding [63]. "
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    • "Similarly, both apo-and holo-lactoferrin has been demonstrated to interact both with canine herpes virus and surface receptors on the Madin-Darby canine kidney cells, thus inhibiting canine herpes virus infection [74]. With regard to the anti-herpes simplex virus 1 ability of lactoferrin, both bovine and human lactoferrin and lactoferricin have demonstrated the ability to block viral entry and also inhibit viral cell-to-cell spread in a dose dependent manner [55] [77] [78] [79], through interaction with negatively charged glycosaminoglycans like heparan sulphate on the cell surface [55] [80] [81] [82] [83] and elements of the viral particle [55]. Differently from herpes simplex virus 1, Marchetti et. "

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