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Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN.
PLoS One. 2014; 9(6):e98785.Plos

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.

Links

Authors+Show Affiliations

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

da Silva Voorham JM

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Torres Pedraza S

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands; Grupo Immunovirología, Universidad de Antioquia, Medellín, Colombia.

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Rodenhuis-Zybert IA

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

MeSH

Cell Adhesion MoleculesCells, CulturedDendritic CellsDengue VirusHumansLectins, C-TypeProtein BindingReceptors, Cell SurfaceVirulence

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24886790

Citation

Richter, Mareike K S., et al. "Immature Dengue Virus Is Infectious in Human Immature Dendritic Cells Via Interaction With the Receptor Molecule DC-SIGN." PloS One, vol. 9, no. 6, 2014, pp. e98785.

Richter MK, da Silva Voorham JM, Torres Pedraza S, et al. Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN. PLoS One. 2014;9(6):e98785.

Richter, M. K., da Silva Voorham, J. M., Torres Pedraza, S., Hoornweg, T. E., van de Pol, D. P., Rodenhuis-Zybert, I. A., Wilschut, J., & Smit, J. M. (2014). Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN. PloS One, 9(6), e98785. https://doi.org/10.1371/journal.pone.0098785

Richter MK, et al. Immature Dengue Virus Is Infectious in Human Immature Dendritic Cells Via Interaction With the Receptor Molecule DC-SIGN. PLoS One. 2014;9(6):e98785. PubMed PMID: 24886790.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN. AU - Richter,Mareike K S, AU - da Silva Voorham,Júlia M, AU - Torres Pedraza,Silvia, AU - Hoornweg,Tabitha E, AU - van de Pol,Denise P I, AU - Rodenhuis-Zybert,Izabela A, AU - Wilschut,Jan, AU - Smit,Jolanda M, Y1 - 2014/06/02/ PY - 2014/02/05/received PY - 2014/05/06/accepted PY - 2014/6/3/entrez PY - 2014/6/3/pubmed PY - 2015/1/21/medline SP - e98785 EP - e98785 JF - PloS one JO - PLoS One VL - 9 IS - 6 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24886790/Immature_dengue_virus_is_infectious_in_human_immature_dendritic_cells_via_interaction_with_the_receptor_molecule_DC_SIGN_ DB - PRIME DP - Unbound Medicine ER -