Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin.
Cell Host Microbe
; 8(2): 186-95, 2010 Aug 19.
Article
en En
| MEDLINE
| ID: mdl-20709295
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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Fiebre del Nilo Occidental
/
Virus del Nilo Occidental
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Complemento C3
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Complemento C4
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Dengue
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Virus del Dengue
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Lectina de Unión a Manosa
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos