Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR.
DC-SIGN and DC-SIGNR are two closely related membrane-associated C-type lectins that bind human immunodeficiency virus (HIV) envelope glycoprotein with high affinity. Binding of HIV to cells expressing DC-SIGN or DC-SIGNR can enhance the efficiency of infection of cells coexpressing the specific HIV receptors. DC-SIGN is expressed on some dendritic cells, while DC-SIGNR is localized to certain endothelial cell populations, including hepatic sinusoidal endothelial cells. We found that soluble versions of the hepatitis C virus (HCV) E2 glycoprotein and retrovirus pseudotypes expressing chimeric forms of both HCV E1 and E2 glycoproteins bound efficiently to DC-SIGN and DC-SIGNR expressed on cell lines and primary human endothelial cells but not to other C-type lectins tested. Soluble E2 bound to immature and mature human monocyte-derived dendritic cells (MDDCs). Binding of E2 to immature MDDCs was dependent on DC-SIGN interactions, while binding to mature MDDCs was partly independent of DC-SIGN, suggesting that other cell surface molecules may mediate HCV glycoprotein interactions. HCV interactions with DC-SIGN and DC-SIGNR may contribute to the establishment or persistence of infection both by the capture and delivery of virus to the liver and by modulating dendritic cell function.
Pöhlmann
Stefan
S
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhang
Jie
J
Baribaud
Frédéric
F
Chen
Zhiwei
Z
Leslie
George J
GJ
Lin
George
G
Granelli-Piperno
Angela
A
Doms
Robert W
RW
Rice
Charles M
CM
McKeating
Jane A
JA
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000821:virology; D006678:HIV / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012995:Solubility; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human; C087035:E1 protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus