West Nile Virus Nonstructural Protein NS1 Inhibits Complement Activation by Binding the Regulatory Protein Factor H

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Nov 30

PMID 17132743

Citations 129

Authors

Kyung Min Chung

M Kathryn Liszewski

Grant Nybakken

Alan E Davis

R Reid Townsend

Daved H Fremont

John P Atkinson

Michael S Diamond

Affiliations

Soon will be listed here.

Abstract

The complement system, by virtue of its dual effector and priming functions, is a major host defense against pathogens. Flavivirus nonstructural protein (NS)-1 has been speculated to have immune evasion activity, because it is a secreted glycoprotein, binds back to cell surfaces, and accumulates to high levels in the serum of infected patients. Herein, we demonstrate an immunomodulatory function of West Nile virus NS1. Soluble and cell-surface-associated NS1 binds to and recruits the complement regulatory protein factor H, resulting in decreased complement activation in solution and attenuated deposition of C3 fragments and C5b-9 membrane attack complexes on cell surfaces. Accordingly, extracellular NS1 may function to minimize immune system targeting of West Nile virus by decreasing complement recognition of infected cells.

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