Sugar and Spice: Viral Envelope-DC-SIGN Interactions in HIV Pathogenesis

DC-SIGN is a calcium dependent lectin that binds to HIV envelope, gp120, with high affinity. Its expression on dendritic cells, coupled with its ability to facilitate the binding and subsequent transfer of virions to permissive T-cells, has led to the hypothesis that DC-SIGN may serve as a conduit the transfer of HIV from the peripheral mucosa to secondary lymphoid organs. Studies have shown that DC-SIGN bound virions can maintain their infectivity for prolonged periods of time despite evidence that DC-SIGN itself may serve as an antigen receptor. How HIV subverts the normal function of DC-SIGN to establish a primary infection in the host is unclear. Therefore, understanding the structural and immunological basis for DCSIGN's function will help us realize the role that DC-SIGN may play in viral transmission and pathogenesis. Importantly, DC-SIGN / envelope interactions may represent a new target for microbicide and vaccine development efforts. Here, we review recent studies on DC-SIGN's structure and function in an effort to present testable models of DC-SIGN's role in HIV pathogenesis.