The mannose receptor mediates dengue virus infection of macrophages

Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2008-02, Vol.4 (2), p.e17-e17
Main Authors: Miller, Joanna L, de Wet, Barend J M, deWet, Barend J M, Martinez-Pomares, Luisa, Radcliffe, Catherine M, Dwek, Raymond A, Rudd, Pauline M, Gordon, Siamon
Format: Article
Language:English
Subjects:
Animals
Antibodies, Blocking
Colleges & universities
Cytokines
Dengue fever
Dengue virus
Dengue Virus - physiology
Fever
Flavivirus
Flow Cytometry
Haplorhini
Homo (Human)
Humans
Immunology
Infectious Diseases
Insects
Interleukin-13 - pharmacology
Interleukin-4 - pharmacology
Lectins, C-Type - physiology
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - metabolism
Leukocytes, Mononuclear - virology
Macrophages - drug effects
Macrophages - virology
Mannose-Binding Lectins - physiology
Mice
Mortality
Mosquitoes
NIH 3T3 Cells
Pathogenesis
Pediatrics
Protein Binding
Receptors, Cell Surface - physiology
Receptors, Virus - metabolism
Recombinant Proteins - metabolism
Software
Vaccines
Viral Envelope Proteins
Viral infections
Virology
Virus Replication
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell-produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.0040017