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 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.
Miller
Joanna L
JL
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
de Wet
Barend J M
BJ
deWet
Barend J M
BJ
Martinez-Pomares
Luisa
L
Radcliffe
Catherine M
CM
Dwek
Raymond A
RA
Rudd
Pauline M
PM
Gordon
Siamon
S
D000818:Animals; D019138:Antibodies, Blocking; D003716:Dengue Virus / Q000502:physiology*; D005434:Flow Cytometry; D000882:Haplorhini; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014759:Viral Envelope Proteins; D014779:Virus Replication
D019138:Antibodies, Blocking; D018793:Interleukin-13; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C111476:dengue virus receptor; D015847:Interleukin-4