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PMID: 16415006 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection.

Journal of virology ·Vol. 80 ·No. 3 ·2006-02-00 ·Pages 1290-301

Davis CW, Nguyen HY, Hanna SL, Sánchez MD, Doms RW, Pierson TC

Abstract

The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high affinity. In vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. In this study, we investigated whether these lectins could enhance cellular infection by West Nile virus (WNV), a mosquito-borne flavivirus related to dengue virus. We discovered that DC-SIGNR promoted WNV infection much more efficiently than did DC-SIGN, particularly when the virus was grown in human cell types. The presence of a single N-linked glycosylation site on either the prM or E glycoprotein of WNV was sufficient to allow DC-SIGNR-mediated infection, demonstrating that uncleaved prM protein present on a flavivirus virion can influence viral tropism under certain circumstances. Preferential utilization of DC-SIGNR was a specific property conferred by the WNV envelope glycoproteins. Chimeras between DC-SIGN and DC-SIGNR demonstrated that the ability of DC-SIGNR to promote WNV infection maps to its carbohydrate recognition domain. WNV virions and subviral particles bound to DC-SIGNR with much greater affinity than DC-SIGN. We believe this is the first report of a pathogen interacting more efficiently with DC-SIGNR than with DC-SIGN. Our results should lead to the discovery of new mechanisms by which these well-studied lectins discriminate among ligands.

MeSH Terms
Animals Binding Sites Cell Adhesion Cell Adhesion Molecules/genetics,physiology Cell Line Cricetinae Glycosylation HeLa Cells Humans Lectins, C-Type/genetics,physiology Ligands Mutation Receptors, Cell Surface/genetics,physiology Recombinant Proteins/genetics,metabolism Viral Envelope Proteins/chemistry,genetics,physiology Virulence West Nile virus/genetics,pathogenicity,physiology
Chemicals
CLEC4M protein, human Cell Adhesion Molecules DC-specific ICAM-3 grabbing nonintegrin Lectins, C-Type Ligands Receptors, Cell Surface Recombinant Proteins Viral Envelope Proteins prM protein, Flavivirus
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Davis Carl W
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Nguyen Hai-Yen
Hanna Sheri L
Sánchez Melissa D
Doms Robert W
Pierson Theodore C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.80.3.1290-1301.2006
Published
2006-02-00
Pages
1290-301
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1346927
Subset
IM
Grants
NIAID NIH HHS · T32 AI007324 · United States
NIAID NIH HHS · U54 AI 57168 · United States
NIAID NIH HHS · T32 AI 07324-13 · United States
NIGMS NIH HHS · T32 GM 007229 · United States
NIAID NIH HHS · T32 AI007632 · United States
NIGMS NIH HHS · T32 GM007229 · United States
NCRR NIH HHS · F31 RR005074 · United States
NIAID NIH HHS · T32 AI 07632 · United States
NIAID NIH HHS · U54 AI057168 · United States
NIAID NIH HHS · AI 50469 · United States
NCRR NIH HHS · F31 RR 05074 · United States
NIAID NIH HHS · R01 AI050469 · United States
External Links
PubMed source DOI: 10.1128/JVI.80.3.1290-1301.2006 PMC Full Text View journal details
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