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-sp ecific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral di ssemination by DC. Abundant expression in lymphoid tissues also implies a f unction for DC-SIGN in chronic HIV-1 infections, in facilitating persistent infection of T cells. We have therefore isolated the rhesus macaque and ch impanzee homologues of DC-SIGN to investigate their function in a primate m odel. 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 abundan tly expressed in lymphoid tissues such as lymph nodes, as well as in mucosa l tissues involved in sexual transmission of HIV-1, and are functionally si milar to human DC-SIGN. They have a high affinity for the immunological lig ands of DC-SIGN: ICAM-2 and -3. Moreover, both homologues bind the HIV-1 en velope glycoprotein gp120 and therefore can act as a HIV-1 trans-receptor i n 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 an d pathogenesis of infection with immunodeficiency viruses. (C) 2001 Elsevie r Science B.V. All rights reserved.