L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus.
Target cell tropism of enveloped viruses is regulated by interactions between viral and cellular factors during transmission, dissemination, and replication within the host. Binding of viral envelope glycoproteins to specific cell-surface receptors determines susceptibility to viral entry. However, a number of cell-surface molecules bind viral envelope glycoproteins without mediating entry. Instead, they serve as capture receptors that disseminate viral particles to target organs or susceptible cells. We and others recently demonstrated that the C type lectins L-SIGN and DC-SIGN capture hepatitis C virus (HCV) by specific binding to envelope glycoprotein E2. In this study, we use an entry assay to demonstrate that HCV pseudoviruses captured by L-SIGN+ or DC-SIGN+ cells efficiently transinfect adjacent human liver cells. Virus capture and transinfection require internalization of the SIGN-HCV pseudovirus complex. In vivo, L-SIGN is largely expressed on endothelial cells in liver sinusoids, whereas DC-SIGN is expressed on dendritic cells. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection.
Cormier
Emmanuel G
EG
Microbiology and Immunology Department, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Durso
Robert J
RJ
Tsamis
Fotini
F
Boussemart
Lise
L
Manix
Catherine
C
Olson
William C
WC
Gardner
Jason P
JP
Dragic
Tatjana
T
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008351:Mannans / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D060225:Tetraspanin 28; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D002738:Chloroquine; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C554798:CD81 protein, human; C433029:CLEC4M protein, human