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Binding of Flavivirus Nonstructural Protein NS1 to C4b Binding Protein Modulates Complement Activation
- Source :
- The Journal of Immunology. 187:424-433
- Publication Year :
- 2011
- Publisher :
- The American Association of Immunologists, 2011.
-
Abstract
- The complement system plays a pivotal protective role in the innate immune response to many pathogens including flaviviruses. Flavivirus nonstructural protein 1 (NS1) is a secreted nonstructural glycoprotein that accumulates in plasma to high levels and is displayed on the surface of infected cells but absent from viral particles. Previous work has defined an immune evasion role of flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 antagonizes complement activation. Dengue, West Nile, or yellow fever virus NS1 directly associated with C4b binding protein (C4BP), a complement regulatory plasma protein that attenuates the classical and lectin pathways. Soluble NS1 recruited C4BP to inactivate C4b in solution and on the plasma membrane. Mapping studies revealed that the interaction sites of NS1 on C4BP partially overlap with the C4b binding sites. Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection.
- Subjects :
- viruses
Immunology
chemical and pharmacologic phenomena
Complement C4b-Binding Protein
Complement receptor
Viral Nonstructural Proteins
Article
Cell Line
Cricetinae
Histocompatibility Antigens
Complement C4b
Animals
Humans
Immunology and Allergy
Complement Activation
Decay-accelerating factor
biology
Complement component 2
CD46
Flavivirus
virus diseases
Dengue Virus
biochemical phenomena, metabolism, and nutrition
Virology
Cell biology
Factor H
biology.protein
Yellow fever virus
West Nile virus
Protein Binding
Complement control protein
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 187
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....4a09c5d3e42287bd0a96277a1d8efbbe