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Journal of Virology, September 2007, p. 9551-9555, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00879-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Antibody Recognition of Cell Surface-Associated NS1 Triggers Fc-{gamma} Receptor-Mediated Phagocytosis and Clearance of West Nile Virus-Infected Cells{triangledown}

Kyung Min Chung,1,5 Bruce S. Thompson,2 Daved H. Fremont,2,3 and Michael S. Diamond1,2,4*

Departments of Medicine,1 Pathology and Immunology,2 Biochemistry and Molecular Biophysics,3 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110,4 Department of Microbiology, Chonbuk National University Medical School, Chonju, Chonbuk 561-180, Republic of Korea5

Received 24 April 2007/ Accepted 5 June 2007

Previous studies have suggested that monoclonal antibodies (MAbs) to flavivirus nonstructural protein-1 (NS-1) protect against infection in mice through an Fc-{gamma} receptor-dependent pathway. To identify a specific mechanism, we evaluated the protective activity of anti-NS1 MAbs to WNV using mice and cells with deficiencies of specific Fc-{gamma} receptors. Our results suggest that only MAbs that recognize cell surface-associated NS1 trigger Fc-{gamma} receptor I- and/or IV-mediated phagocytosis and clearance of WNV-infected cells. These findings may be relevant for generating novel therapeutic MAbs or vaccines against flaviviruses that target the NS1 protein.


* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail: diamond{at}borcim.wustl.edu

{triangledown} Published ahead of print on 20 June 2007.


Journal of Virology, September 2007, p. 9551-9555, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00879-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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