title: Antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate.
abstract: Human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. We used alphaviruses, adapted to interaction with heparan sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral activity. Lactoferrin inhibited infection of BHK-21 cells by HS-adapted, but not by non-adapted, Sindbis virus (SIN) or Semliki Forest virus (SFV). Lactoferrin also inhibited binding of radiolabeled HS-adapted viruses to BHK-21 cells or liposomes containing lipid-conjugated heparin as a receptor analog. On the other hand, low-pH-induced fusion of the viruses with liposomes, which occurs independently of virus-receptor interaction, was unaffected. Studies involving preincubation of virus or cells with lactoferrin suggested that the protein does not bind to the virus, but rather blocks HS-moieties on the cell surface. Charge-modified human serum albumin, with a net positive charge, had a similar antiviral effect against HS-adapted SIN and SFV, suggesting that the antiviral activity of lactoferrin is related to its positive charge. It is concluded that human lactoferrin inhibits viral infection by interfering with virus-receptor interaction rather than by affecting subsequent steps in the viral cell entry or replication processes.
authors.affiliation: Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Barry-Lee
authors.initials: BL
authors.lastname: Waarts
authors.forename: Onwuchekwa J C
authors.initials: OJ
authors.lastname: Aneke
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: Smit
authors.forename: Koji
authors.initials: K
authors.lastname: Kimata
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.forename: Dirk K F
authors.initials: DK
authors.lastname: Meijer
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000494:pharmacology*; D008081:Liposomes; D008561:Membrane Fusion / Q000187:drug effects; D011991:Receptors, Virus / Q000187:drug effects; D012672:Semliki forest virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D012709:Serum Albumin / Q000494:pharmacology; D012845:Sindbis Virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D006497:Heparan Sulfate; D007781:Lactoferrin; D008081:Liposomes; D011991:Receptors, Virus; D012709:Serum Albumin