title: C-type lectin Mermaid inhibits dendritic cell mediated HIV-1 transmission to CD4+ T cells.
abstract: Dendritic cells (DCs) are important in HIV-1 transmission; DCs capture invading HIV-1 through the interaction of the gp120 oligosaccharides with the C-type lectin DC-SIGN and migrate to the lymphoid tissues where HIV-1 is transmitted to T cells. Thus, the HIV-1 envelope glycoprotein gp120 is an attractive target to prevent interactions with DCs and subsequent viral transmission. Here, we have investigated whether the structural homologue of DC-SIGN, the nematode C-type lectin Mermaid can be used to prevent HIV-1 transmission by DCs. Our data demonstrate that Mermaid interacts with high mannose structures present on HIV-1 gp120 and thereby inhibits HIV-1 binding to DC-SIGN on DCs. Moreover, Mermaid inhibits DC-SIGN-mediated HIV-1 transmission from DC to T cells. We have identified Mermaid as a non-cytotoxic agent that shares the glycan specificity with DC-SIGN and inhibits DC-SIGN-gp120 interaction. The results are important for the anti-HIV-1 microbicide development directed at preventing DC-HIV-1 interactions.
authors.affiliation: Department of Molecular Cellular Biology and Immunology, VU University Medical Center, vd Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Nabatov
authors.forename: Marein A W P
authors.initials: MA
authors.lastname: de Jong
authors.forename: Lot
authors.initials: L
authors.lastname: de Witte
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulgheresi
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D015801:Helminth Proteins / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D009348:Nematoda; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D053585:Virus Attachment; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D019380:Anti-HIV Agents; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D015801:Helminth Proteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin