DC-SIGN, a cell surface C-type lectin expressed on dendritic cells (DCs), is thought to play key roles in the interaction of DCs with T cells as well as in human immunodeficiency virus (HIV) pathogenesis (reviewed in reference 4). By binding to intracellular adhesion molecule 3 (ICAM-3), DC-SIGN facilitates the initial interaction between DCs and resting T cells, which leads to antigen recognition and initiation of the immune response (6). DC-SIGN is also a unique type of attachment factor for HIV type 1 (HIV-1) in that it binds the envelope glycoprotein gp120 of HIV-1 and promotes infection in trans of target CD4+ T cells (5). It is believed that HIV may exploit DC-SIGN for its transport from mucosal sites of infection to permissive T cells in secondary lymphoid organs. DC-SIGN also binds HIV-2 and simian immunodeficiency virus surface glycoproteins (10) and can enhance infection in cis, especially when CD4 and coreceptor levels are limiting (7). We were thus interested to study potential DC-SIGN interaction with feline immunodeficiency virus (FIV), the causative agent of feline AIDS in the domestic cat (8). Feline DC-SIGN has not been cloned, and reagents and protocols for the preparation of feline DCs are in development. However, based on a previous demonstration of FIV binding to human CXCR4 (13), we initiated studies utilizing human DC-SIGN.