Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

T. B. Geijtenbeek, G. Koopman, G. C. van Duijnhoven, S. J. van Vliet, A. C. van Schijndel, A. Engering, J. L. Heeney, Y. van Kooyk

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Abstract

Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a function for DC-SIGN in chronic HIV-1 infections, in facilitating persistent infection of T cells. We have therefore isolated the rhesus macaque and chimpanzee homologues of DC-SIGN to investigate their function in a primate model. Both rhesus macaque and chimpanzee DC-SIGN are highly similar to the human homologue. Three monoclonal antibodies against human DC-SIGN, AZN-D1, -D2 and -D3, cross-react with rhesus macaque DC-SIGN, whereas AZN-D2 does not cross-react with chimpanzee DC-SIGN. The primate homologues are abundantly expressed in lymphoid tissues such as lymph nodes, as well as in mucosal tissues involved in sexual transmission of HIV-1, and are functionally similar to human DC-SIGN. They have a high affinity for the immunological ligands of DC-SIGN: ICAM-2 and -3. Moreover, both homologues bind the HIV-1 envelope glycoprotein gp120 and therefore can act as a HIV-1 trans-receptor in the same way as human DC-SIGN. These data demonstrate that primate models are suitable to further dissect the role of DC-SIGN in the transmission and pathogenesis of infection with immunodeficiency viruses
Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalImmunology letters
Volume79
Issue number1-2
DOIs
Publication statusPublished - 1 Nov 2001

Keywords

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • Cell Adhesion Molecules
  • Cross Reactions
  • DNA, Complementary/genetics
  • Dendritic Cells/immunology
  • Gene Expression
  • HIV Envelope Protein gp120/immunology
  • HIV Infections/immunology
  • HIV-1/immunology
  • Humans
  • Lectins, C-Type
  • Lectins/genetics
  • Ligands
  • Macaca mulatta/genetics
  • Membrane Glycoproteins
  • Molecular Sequence Data
  • Pan troglodytes/genetics
  • Receptors, Cell Surface/genetics
  • Receptors, HIV/genetics
  • Sequence Homology, Amino Acid
  • Simian Immunodeficiency Virus/immunology
  • Species Specificity
  • Viral Envelope Proteins

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