Publication: Antagonism of the complement component C4 by flavivirus nonstructural protein NS1
Issued Date
2010-04-12
Resource Type
ISSN
15409538
00221007
00221007
Other identifier(s)
2-s2.0-77951063838
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Experimental Medicine. Vol.207, No.4 (2010), 793-806
Suggested Citation
Panisadee Avirutnan, Anja Fuchs, Richard E. Hauhart, Pawit Somnuke, Soonjeon Youn, Michael S. Diamond, John P. Atkinson Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. Journal of Experimental Medicine. Vol.207, No.4 (2010), 793-806. doi:10.1084/jem.20092545 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/29242
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Antagonism of the complement component C4 by flavivirus nonstructural protein NS1
Other Contributor(s)
Abstract
The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection. © 2010 Avirutnan et al.