title: Beyond attachment: Roles of DC-SIGN in dengue virus infection.
abstract: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used 4 cell types: human immature dendritic cells and NIH3T3 cells expressing either wild-type DC-SIGN or 2 internalization-deficient DC-SIGN mutants, in which either the 3 cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated. Using confocal and super-resolution imaging and high content single particle tracking, we investigated DENV binding, DC-SIGN surface transport, endocytosis, as well as cell infectivity. DC-SIGN was found colocalized with DENV inside cells suggesting hand-off at the plasma membrane to another receptor did not occur. Moreover, all 3 DC-SIGN molecules on NIH3T3 cells supported cell infection. These results imply the involvement of a co-receptor because cells expressing the internalization-deficient mutants could still be infected.
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Marc
authors.initials: M
authors.lastname: Ridilla
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Pratik
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Laurie
authors.initials: L
authors.lastname: Betts
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Emily
authors.initials: E
authors.lastname: Gallichotte
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Lidea
authors.initials: L
authors.lastname: Shahidi
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Thompson
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Ken
authors.initials: K
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D003715:Dengue / Q000378:metabolism* / Q000821:virology*; D003716:Dengue Virus / Q000472:pathogenicity*; D004705:Endocytosis / Q000502:physiology; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: 
  DC-SIGN
  ; C-type lectin receptor; antigen-presenting cells; dengue virus; fluorescence microscopy; in vivo trafficking; quantitative colocalization; super-resolution imaging; viral entry; viral receptor