A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection

The discovery of dendritic cell (DC)-specific intercellular adhesion molecu le (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A r elated molecule called DC-SIGNR exhibits 77% amino acid sequence identity w ith DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on ch romosome 19p13.2-3. Their strong homology and close physical location indic ate a recent duplication of the original gene. Messenger RNA and protein ex pression patterns demonstrate that the DC-SIGN-related, molecule is highly expressed on Liver sinusoidal cells and in the lymph node but not on DCs, i ll contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN-related molecule is L-SIGN, liver/lymph node-specific ICAM- 3-grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by s inusoidal endothelial cells. Functional studies indicate that L-SIGN behave s similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in tra ns. We propose that L-SIGN may play an important role in the interaction be tween liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.