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Original Article

^a Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick,
^b Intramural Research Support Program, Science Applications International Corporation-Frederick,
^c HIV Drug Resistance Program, National Cancer Institute-Frederick, Frederick, Maryland 21702
^d Tumor Immunology Department, University Medical Center St. Radbound, Nijmegen 6525 EX, The Netherlands
^e Zentrum für Moleculare Biologie Heidelberg (ZMBH), D-69120 Heidelberg, Germany
P.O. Box B, NCI-FCRDC, Frederick, MD 21702.301-846-1909301-846-1390

carringt{at}mail.ncifcrf.gov

The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (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 related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN–related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in 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 sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves 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 trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.

Key Words: L-SIGN • adhesion receptor • chromosome 19p13.2-3 • ICAM-3 • HIV-1 gp120

Abbreviations used in this paper: CCR, CC chemokine receptor; DC, dendritic cell; DC-SIGN, DC-specific ICAM-3–grabbing nonintegrin; EST, expressed sequence tag; ICAM, intercellular adhesion molecule; L-SIGN, liver/lymph node–specific ICAM-3–grabbing nonintegrin; LSEC, liver sinusoidal endothelial cell; nt, nucleotides; RH, radiation hybrid; RT, reverse transcription; UTR, untranslated region.

© 2001 The Rockefeller University Press

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