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 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.
Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Frederick, MD 21702, USA.
A A
AA
Bashirova
T B
TB
Geijtenbeek
G C
GC
van Duijnhoven
S J
SJ
van Vliet
J B
JB
Eilering
M P
MP
Martin
L
L
Wu
T D
TD
Martin
N
N
Viebig
P A
PA
Knolle
V N
VN
KewalRamani
Y
Y
van Kooyk
M
M
Carrington
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018076:DNA, Complementary; D003713:Dendritic Cells; D004727:Endothelium / Q000166:cytology; D005091:Exons; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D037181:Lectins, C-Type; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011946:Receptors, Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D015699:HIV Envelope Protein gp120; D037102:Lectins; D037181:Lectins, C-Type; D011946:Receptors, Antigen; D011956:Receptors, Cell Surface; D015728:Receptors, HIV; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human; C483616:ICAM3 protein, human