Dendritic cells (DCs) that control immune responses were recently found to capture and transport HIV from the mucosal area to remote lymph nodes, where DCs hand over HIV to CD4+ T lymphocytes. DCs also amplify the amount of virus and extend the duration of viral infectivity. Multiple strains of HIV-1, HIV-2 and SIV bind to DCs via DC-SIGN. ICAM-3 is the natural ligand for DC-SIGN. A DC-SIGN homologue (termed DC-SIGNR, L-SIGN, and DC-SIGN2) was identified recently. DC-SIGN forms a novel gene family with DC-SIGNR and many alternatively spliced isoforms of DC-SIGN and DC-SIGNR. The expression of DC-SIGN was found in mucosal tissues including placenta, small intestine, and rectum.