Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 50, Pages 19111-19116Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0605668103
Keywords
flavivirus; immune evasion; innate immunity; pathogenesis
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Funding
- NIAID NIH HHS [U54 AI057160, U54 AI 057160] Funding Source: Medline
- NIDDK NIH HHS [P30 DK 52574, P30 DK052574] Funding Source: Medline
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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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