The Mannose Receptor Mediates Dengue Virus Infection of Macrophages

PLoS Pathogens

Raymond A Dwek¹  Pauline M Rudd¹  Catherine M Radcliffe¹  Luisa Martinez-Pomares²  Joanna L Miller³  Barend J. M deWet³  Siamon Gordon³ 

[1] Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom;School of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom;Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

关键词: Antibodies;    Cell binding;    Enzyme-linked immunoassays;    Cytokines;    Monocytes;    Mannose;    Protein domains;    Macrophages;   

DOI  :  10.1371/journal.ppat.0040017

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY