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

53 Scopus citations


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
Issue number2
StatePublished - Aug 19 2010


ASJC Scopus subject areas

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

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