DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission.
The dendritic cell (DC)-specific HIV-1 receptor DC-SIGN plays a key-role in the dissemination of HIV-1 by DCs. DC-SIGN captures HIV-1 at sites of entry, enabling its transport to lymphoid tissues, where DC-SIGN efficiently transmits low amounts of HIV-1 to T cells. The expression pattern of DC-SIGN in mucosal tissue, lymph nodes, placenta and blood suggests a function for DC-SIGN in both horizontal and vertical transmission of HIV-1. Moreover, the efficiency of DC-SIGN+ blood DC to transmit HIV-1 to T cells supports a role in HIV-1 transmission via blood. To date, DC-SIGN represents a novel class of HIV-1 receptor, because it does not allow viral infection but binds HIV-1 and enhances its infection of T cells in trans. Its unique function is further underscored by its restricted expression on DCs. Although DC-SIGN is a C-type lectin with an affinity for carbohydrates exemplified by its interaction with its immunological ligand ICAM-3, recent evidence demonstrates that glycosylation of gp120 is not necessary for its interaction with DC-SIGN. Moreover, mutational analysis demonstrates that the HIV-1 gp120 binding site in DC-SIGN is different from that of ICAM-3. Besides its role in DC-mediated adhesion processes, DC-SIGN also functions as an antigen receptor that captures and internalises antigens for presentation by DC. Strikingly, HIV-1 circumvents processing after binding DC-SIGN and remains infectious for several days after capture. A better understanding of the action of this novel HIV receptor in initial viral infection and subsequent transmission will provide a basis for the design of drugs that inhibit or alter interactions of DC-SIGN with gp120, interfering with HIV-1 dissemination and that may have a therapeutic value in both immunological diseases and/or HIV-1 infections.
Geijtenbeek
T B H
TB
Department of Molecular Cell Biology, Vrije Universiteit Medical Center Amsterdam, van de Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
van Kooyk
Y
Y
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D015658:HIV Infections; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D011323:Primates; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D011991:Receptors, Virus / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human