Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN.
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.
Geijtenbeek
T B
TB
Department of Molecular Cell Biology, Vrjie University Medical Centre Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. t.geijtenbeek.cell@med.vu.nl
Koopman
G
G
van Duijnhoven
G C
GC
van Vliet
S J
SJ
van Schijndel
A C
AC
Engering
A
A
Heeney
J L
JL
van Kooyk
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D003429:Cross Reactions; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015728:Receptors, HIV / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013045:Species Specificity; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D015699:HIV Envelope Protein gp120; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D015728:Receptors, HIV; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C069623:gp120 protein, Simian immunodeficiency virus