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

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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. © 2005 Elsevier Inc. All rights reserved.

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Waarts, B. L., Aneke, O. J. C., Smit, J. M., Kimata, K., Bittman, R., Meijer, D. K. F., & Wilschut, J. (2005). Antiviral activity of human lactoferrin: Inhibition of alphavirus interaction with heparan sulfate. Virology, 333(2), 284–292. https://doi.org/10.1016/j.virol.2005.01.010

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