Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN

PLoS One. 2014 Jun 2;9(6):e98785. doi: 10.1371/journal.pone.0098785. eCollection 2014.

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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Dendritic Cells / virology*
  • Dengue Virus / pathogenicity*
  • Humans
  • Lectins, C-Type / metabolism*
  • Protein Binding
  • Receptors, Cell Surface / metabolism*
  • Virulence

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface

Grants and funding

This work was supported by the Dutch Organization for Scientific research (NWO- Earth and Life Sciences (grant to JMS) and NWO-ZonMW AGIKO (grant to JW) and by the University Medical Center Groningen (grant to MKSR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.