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

• Published in: PloS one 2014-06, Vol.9 (6), p.e98785-e98785
• Main Authors: Richter, Mareike K S, da Silva Voorham, Júlia M, Torres Pedraza, Silvia, Hoornweg, Tabitha E, van de Pol, Denise P I, Rodenhuis-Zybert, Izabela A, Wilschut, Jan, Smit, Jolanda M
• Format: Article
• Language: English
• Subjects: Antibodies; Aquatic insects; Biology and Life Sciences; Cell Adhesion Molecules - metabolism; Cell culture; Cells, Cultured; DC-SIGN protein; Dendritic cells; Dendritic Cells - virology; Dengue; Dengue fever; Dengue Virus - pathogenicity; Flow cytometry; Glycoproteins; Health aspects; Humans; Immunoglobulins; Infection; Infections; Infectious diseases; Infectivity; Lectins, C-Type - metabolism; Macrophages; Medicine and Health Sciences; Monocytes; Pathogenesis; Penicillin; Protein Binding; Proteins; Receptors, Cell Surface - metabolism; Rodents; Vector-borne diseases; Viral diseases; Virions; Virulence; Viruses; West Nile virus
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098785

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. 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. 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.