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DC-SIGN: A Novel HIV Receptor on DCs That Mediates HIV-1 Transmission

  • T. B. H. Geijtenbeek
  • Y. van Kooyk
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 276)

Abstract

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.

Keywords

Human Immunodeficiency Virus Type Simian Immunodeficiency Virus Liver Sinusoidal Endothelial Cell Dendritic Cell Precursor Gp120 Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • T. B. H. Geijtenbeek
    • 1
  • Y. van Kooyk
    • 1
  1. 1.Department of Molecular Cell BiologyVrije Universiteit Medical Center AmsterdamAmsterdamThe Netherlands

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