title: Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN.
abstract: BACKGROUND
  Dengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Important target cells during DENV infection are macrophages, monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to secrete a large number of partially immature and fully immature particles alongside mature virions. Fully immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection.
  
  
  RESULTS
  In this study, we re-evaluated the infectious properties of fully immature particles in absence and presence of anti-DENV human serum. We show that immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we demonstrate that immature dendritic cells, in contrast to macrophage-like cells, do not support antibody-dependent enhancement of immature DENV.
  
  
  CONCLUSIONS
  Our data shows that immature DENV can infect imDCs through interaction with DC-SIGN, suggesting that immature and partially immature DENV particles may contribute to dengue pathogenesis during primary infection. Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs we propose that macrophages/monocytes rather than imDCs contribute to the increased viral load observed during severe heterotypic DENV re-infections.
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Mareike K S
authors.initials: MK
authors.lastname: Richter
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Júlia M
authors.initials: JM
authors.lastname: da Silva Voorham
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands; Grupo Immunovirología, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Torres Pedraza
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tabitha E
authors.initials: TE
authors.lastname: Hoornweg
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Denise P I
authors.initials: DP
authors.lastname: van de Pol
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Izabela A
authors.initials: IA
authors.lastname: Rodenhuis-Zybert
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
authors.affiliation: Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: Smit
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D003716:Dengue Virus / Q000472:pathogenicity*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014774:Virulence; 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