Antiviral activity of human lactoferrin: Inhibition of alphavirus interaction with heparan sulfate

  • Waarts B
  • Aneke O
  • Smit J
 et al. 
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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. © 2005 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Antiviral
  • Heparan sulfate
  • Lactoferrin
  • Liposome
  • Receptor
  • Semliki Forest virus
  • Sindbis virus

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  • Barry Lee Waarts

  • Onwuchekwa J.C. Aneke

  • Jolanda M. Smit

  • Koji Kimata

  • Robert Bittman

  • Dirk K.F. Meijer

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