Lactoferrin prevents dendritic cell-mediated human immunodeficiency virus type 1 transmission by blocking the DC-SIGN--gp120 interaction.
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.
Groot
Fedde
F
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Geijtenbeek
Teunis B H
TB
Sanders
Rogier W
RW
Baldwin
Christopher E
CE
Sanchez-Hernandez
Marta
M
Floris
René
R
van Kooyk
Yvette
Y
de Jong
Esther C
EC
Berkhout
Ben
B
D000818:Animals; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000502:physiology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000502:physiology*; D013045:Species Specificity; D014779:Virus Replication / Q000187:drug effects; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D007781:Lactoferrin; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin