Inhibition of herpes simplex virus infection by lactoferrin is dependent on interference with the virus binding to glycosaminoglycans.

• Previous reports have indicated that lactoferrin inhibits herpes simplex virus (HSV) infection during the very early phases of the viral replicative cycle. In the present work we investigated the mechanism of the antiviral activity of lactoferrin in mutant glycosaminoglycan (GAG)-deficient cells. Bovine lactoferrin (BLf) was a strong inhibitor of HSV-1 infection in cells expressing either heparan sulfate (HS) or chondroitin sulfate (CS) or both, but was ineffective or less efficient in GAG-deficient cells or in cells treated with GAG-degrading enzymes. In contrast to wild-type HSV-1, virus mutants devoid of glycoprotein C (gC) were significantly less inhibited by lactoferrin in GAG-expressing cells, indicating that lactoferrin interfered with the binding of viral gC to cell surface HS and/or CS. Finally, we demonstrated that lactoferrin bound directly to both HS and CS isolated from surfaces of the studied cells, as well as to commercial preparations of GAG chains. The results support the hypothesis that the inhibition of HSV-1 infectivity by lactoferrin is dependent on its interaction with cell surface GAG chains of HS and CS.

Nyckelord

Animals

Antiviral Agents

metabolism

pharmacology

Cattle

Cells

Cultured

Chondroitin Sulfates

metabolism

Fibroblasts

drug effects

virology

Glycosaminoglycans

chemistry

metabolism

Heparitin Sulfate

metabolism

Herpesvirus 1

Human

drug effects

metabolism

pathogenicity

Humans

L Cells (Cell Line)

Lactoferrin

metabolism

pharmacology

Mice

Viral Envelope Proteins

metabolism

Publikations- och innehållstyp

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