Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin

Anja Fuchs, Tsai Yu Lin, David Beasley, Cordula M. Stover, Wilhelm J. Schwaeble, Theodore C. Pierson, Michael S. Diamond

Research output: Contribution to journalArticle

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Abstract

An intact complement system is crucial for limiting West Nile virus (WNV) dissemination. Herein, we define how complement directly restricts flavivirus infection in an antibody-independent fashion. Mannose-binding lectin (MBL) recognized N-linked glycans on the structural proteins of WNV and Dengue virus (DENV), resulting in neutralization through a C3- and C4-dependent mechanism that utilized both the canonical and bypass lectin activation pathways. For WNV, neutralization occurred with virus produced in insect cells, whereas for DENV, neutralization of insect and mammalian cell-derived virus was observed. Mechanism of action studies suggested that the MBL-dependent neutralization occurred, in part, by blocking viral fusion. Experiments in mice showed an MBL-dependent accelerated intravascular clearance of DENV or a WNV mutant with two N-linked glycans on its E protein, but not with wild-type WNV. Our studies show that MBL recognizes terminal mannose-containing carbohydrates on flaviviruses, resulting in neutralization and efficient clearance in vivo.

Original languageEnglish (US)
Pages (from-to)186-195
Number of pages10
JournalCell Host and Microbe
Volume8
Issue number2
DOIs
StatePublished - Aug 19 2010

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Flavivirus Infections
Mannose-Binding Lectin
West Nile virus
Polysaccharides
Dengue Virus
Insects
Viruses
Flavivirus
Mannose
Lectins
Proteins
Carbohydrates
Antibodies

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin. / Fuchs, Anja; Lin, Tsai Yu; Beasley, David; Stover, Cordula M.; Schwaeble, Wilhelm J.; Pierson, Theodore C.; Diamond, Michael S.

In: Cell Host and Microbe, Vol. 8, No. 2, 19.08.2010, p. 186-195.

Research output: Contribution to journalArticle

Fuchs, Anja ; Lin, Tsai Yu ; Beasley, David ; Stover, Cordula M. ; Schwaeble, Wilhelm J. ; Pierson, Theodore C. ; Diamond, Michael S. / Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin. In: Cell Host and Microbe. 2010 ; Vol. 8, No. 2. pp. 186-195.
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