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Transcript
LACTOFERRIN MODULATES HSV-1 INFECTION AT EARLY STAGES OF
THE VIRAL LIFE CYCLE AND THIS IS A TEST ABSTRACT
Välimaa H1,2, Hukkanen V1, Waris M1, Tenovuo J2
1
Department of Virology, 2Department of Cariology, University of Turku, Turku, Finland
The abstract should describe the purpose of the study and the major results and conclusions. If you
prefer breaking the text into paragraphs, please do not leave space between them.
Oral mucosa is a frequent site of primary herpes simplex virus (HSV) type 1 infection. However,
although intraoral shedding of HSV is common, clinical signs of reactivation are far more frequently
observed at extraoral compared to intraoral sites, suggesting that reactivation may be inhibited by the
intraoral environment. We have previously shown that salivary neutralization activity of HSV correlates
with concentration of lactoferrin (an iron-binding glycoprotein) in asymptomatic HSV seropositive
subjects. In the current study, we investigated further the mechanism of lactoferrin-mediated inhibition of
HSV-1 infection. These studies show that lactoferrin is effective in blocking HSV infection at physiological
concentrations. Preincubation of HSV virions with lactoferrin significantly decreased HSV infectivity at
higher concentrations. Presence of lactoferrin during either the viral absorption period or the entire HSV
infection cycle inhibited HSV in a dose-dependent manner. Wild type HSV was more sensitive to
inhibition compared to HSV gC-39, a gC-negative strain of HSV-1, suggesting a mechanism of lactoferrin
interference with gC-heparan sulfate binding at the initial attachment of HSV virion to the cell surface.
Interestingly, an incomplete monolayer of keratinocytes on rafts at the time of viral inoculation enabled a
more efficient production of infectious virus as assessed by the amount of progeny virus in raft
homogenates. Our results suggest that lactoferrin is a critical component of the innate immune response
that can efficiently modulate the infectivity of HSV in the oral environment, possibly by interference with
early stages of infection.