TY - JOUR
T1 - Measles virus targets DC-SIGN to enhance dendritic cell infection
AU - de Witte, Lot
AU - Abt, Marion
AU - Schneider-Schaulies, Sibylle
AU - van Kooyk, Yvette
AU - Geijtenbeek, Teunis B H
PY - 2006/4
Y1 - 2006/4
N2 - Dendritic cells (DCs) are involved in the pathogenesis of measles virus (MV) infection by inducing immune suppression and possibly spreading the virus from the respiratory tract to lymphatic tissues. It is becoming evident that DC function can be modulated by the involvement of different receptors in pathogen interaction. Therefore, we have investigated the relative contributions of different MV-specific receptors on DCs to MV uptake into and infection of these cells. DCs express the MV receptors CD46 and CD150, and we demonstrate that the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a novel receptor for laboratory-adapted and wild-type MV strains. The ligands for DC-SIGN are both MV glycoproteins F and H. In contrast to CD46 and CD150, DC-SIGN does not support MV entry, since DC-SIGN does not confer susceptibility when stably expressed in CHO cells. However, DC-SIGN is important for the infection of immature DCs with MV, since both attachment and infection of immature DCs with MV are blocked in the presence of DC-SIGN inhibitors. Our data demonstrate that DC-SIGN is crucial as an attachment receptor to enhance CD46/CD150-mediated infection of DCs in cis. Moreover, MV might not only target DC-SIGN to infect DCs but may also use DC-SIGN for viral transmission and immune suppression.
AB - Dendritic cells (DCs) are involved in the pathogenesis of measles virus (MV) infection by inducing immune suppression and possibly spreading the virus from the respiratory tract to lymphatic tissues. It is becoming evident that DC function can be modulated by the involvement of different receptors in pathogen interaction. Therefore, we have investigated the relative contributions of different MV-specific receptors on DCs to MV uptake into and infection of these cells. DCs express the MV receptors CD46 and CD150, and we demonstrate that the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a novel receptor for laboratory-adapted and wild-type MV strains. The ligands for DC-SIGN are both MV glycoproteins F and H. In contrast to CD46 and CD150, DC-SIGN does not support MV entry, since DC-SIGN does not confer susceptibility when stably expressed in CHO cells. However, DC-SIGN is important for the infection of immature DCs with MV, since both attachment and infection of immature DCs with MV are blocked in the presence of DC-SIGN inhibitors. Our data demonstrate that DC-SIGN is crucial as an attachment receptor to enhance CD46/CD150-mediated infection of DCs in cis. Moreover, MV might not only target DC-SIGN to infect DCs but may also use DC-SIGN for viral transmission and immune suppression.
KW - Animals
KW - Antigens, CD/metabolism
KW - CHO Cells
KW - Cell Adhesion Molecules/genetics
KW - Cricetinae
KW - Dendritic Cells/cytology
KW - Enzyme-Linked Immunosorbent Assay
KW - Flow Cytometry
KW - Fluorescein-5-isothiocyanate
KW - Fluorescent Antibody Technique, Indirect
KW - Fluorescent Dyes
KW - Green Fluorescent Proteins/metabolism
KW - Humans
KW - K562 Cells
KW - Lectins, C-Type/genetics
KW - Ligands
KW - Measles/virology
KW - Measles virus/genetics
KW - Membrane Cofactor Protein/metabolism
KW - Membrane Glycoproteins/genetics
KW - Receptors, Cell Surface/genetics
KW - Viral Fusion Proteins/metabolism
U2 - 10.1128/JVI.80.7.3477-3486.2006
DO - 10.1128/JVI.80.7.3477-3486.2006
M3 - Article
C2 - 16537615
VL - 80
SP - 3477
EP - 3486
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 7
ER -