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Journal of Virology, March 2005, p. 3009-3015, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3009-3015.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Lactoferrin Prevents Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission by Blocking the DC-SIGN—gp120 Interaction

Fedde Groot,1,2 Teunis B. H. Geijtenbeek,3 Rogier W. Sanders,1 Christopher E. Baldwin,1 Marta Sanchez-Hernandez,3 René Floris,4 Yvette van Kooyk,3 Esther C. de Jong,2 and Ben Berkhout1*

Department of Human Retrovirology,1 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam,2 Department of Molecular Cell Biology and Immunology, Vrÿe Universiteit Medical Center, Amsterdam,3 Department of Product Technology, NIZO Food Research, Ede, The Netherlands4

Received 6 August 2004/ Accepted 15 October 2004

One of the cell types first encountered by human immunodeficiency virus type 1 (HIV-1) following sexual transmission are dendritic cells (DC). DC capture HIV-1 through C-type lectin receptors, of which the best studied example is DC-SIGN, which mediates HIV-1 internalization. DC can keep the virus infectious for several days and are able to transmit HIV-1 to CD4+ T cells. We tested proteins from milk and serum for their ability to block DC-mediated HIV-1 transmission, of which bovine lactoferrin (bLF) is the most potent inhibitor. bLF binds strongly to DC-SIGN, thus preventing virus capture and subsequent transmission. Interestingly, bLF is a much more efficient inhibitor of transmission than human lactoferrin. Since bLF is nontoxic and easy to purify in large quantities, it is an interesting candidate microbicide against HIV-1. Another advantage of bLF is its ability to block HIV-1 replication in T cells. DC-mediated capture of a bLF-resistant HIV-1 variant that was selected during long-term culturing in T cells could still be blocked by bLF. This underscores the usefulness of bLF as a microbicide drug to prevent HIV-1 transmission.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Phone: 31-30-5664822. Fax: 31-20-5669064. E-mail: b.berkhout{at}amc.uva.nl.

Journal of Virology, March 2005, p. 3009-3015, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3009-3015.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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