Human lactoferrin but not lysozyme neutralizes HSV-1 and inhibits HSV-1 replication and cell-to-cell spread.
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.
Institute of Dentistry, University of Turku, Turku, Finland. hannamari.valimaa@helsinki.fi
Hannamari
H
Välimaa
Jorma
J
Tenovuo
Matti
M
Waris
Veijo
V
Hukkanen
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D006561:Herpes Simplex / Q000276:immunology / Q000635:transmission* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D007781:Lactoferrin / Q000276:immunology*; D009113:Muramidase / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D014709:Vero Cells; D014779:Virus Replication
D023181:Antimicrobial Cationic Peptides; D009113:Muramidase; D007781:Lactoferrin