L-SIGN (CD209L) isoforms differently mediate trans-infection of hepatoma cells by hepatitis C virus pseudoparticles.
L-SIGN is a C-type lectin that is expressed on liver sinusoidal endothelial cells. Capture of Hepatitis C virus (HCV) by this receptor results in trans-infection of hepatoma cells. L-SIGN alleles have been identified that encode between three and nine tandem repeats of a 23 residue stretch in the juxtamembrane oligomerization domain. Here, it was shown that these repeat-region isoforms are expressed at the surface of mammalian cells and variably bind HCV envelope glycoprotein E2 and HCV pseudoparticles. Differences in binding were reflected in trans-infection efficiency, which was highest for isoform 7 and lowest for isoform 3. These findings provide a molecular mechanism whereby L-SIGN polymorphism could influence the establishment and progression of HCV infection.
Falkowska
Emilia
E
Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Durso
Robert J
RJ
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Gardner
Jason P
JP
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Cormier
Emmanuel G
EG
Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Arrigale
Robert A
RA
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Ogawa
Raymond N
RN
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Donovan
Gerald P
GP
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Maddon
Paul J
PJ
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Olson
William C
WC
Progenics Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Dragic
Tatjana
T
Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000209:etiology* / Q000235:genetics / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D018598:Minisatellite Repeats; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000502:physiology
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus