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Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms.
Chung, Kyung Min; Nybakken, Grant E; Thompson, Bruce S; Engle, Michael J; Marri, Anantha; Fremont, Daved H; Diamond, Michael S.
Afiliação
  • Chung KM; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
J Virol ; 80(3): 1340-51, 2006 Feb.
Article em En | MEDLINE | ID: mdl-16415011
ABSTRACT
The flavivirus nonstructural protein NS1 is a highly conserved secreted glycoprotein that does not package with the virion. Immunization with NS1 elicits a protective immune response against yellow fever, dengue, and tick-borne encephalitis flaviviruses through poorly defined mechanisms. In this study, we purified a recombinant, secreted form of West Nile virus (WNV) NS1 glycoprotein from baculovirus-infected insect cells and generated 22 new NS1-specific monoclonal antibodies (MAbs). By performing competitive binding assays and expressing truncated NS1 proteins on the surface of yeast (Saccharomyces cerevisiae) and in bacteria, we mapped 21 of the newly generated MAbs to three NS1 fragments. Prophylaxis of C57BL/6 mice with any of four MAbs (10NS1, 14NS1, 16NS1, and 17NS1) strongly protected against lethal WNV infection (75 to 95% survival, respectively) compared to saline-treated controls (17% survival). In contrast, other anti-NS1 MAbs of the same isotype provided no significant protection. Notably, 14NS1 and 16NS1 also demonstrated marked efficacy as postexposure therapy, even when administered as a single dose 4 days after infection. Virologic analysis showed that 17NS1 protects at an early stage in infection through a C1q-independent and Fc gamma receptor-dependent pathway. Interestingly, 14NS1, which maps to a distinct region on NS1, protected through a C1q- and Fc gamma receptor-independent mechanism. Overall, our data suggest that distinct regions of NS1 can elicit protective humoral immunity against WNV through different mechanisms.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND / 4_TD Base de dados: MEDLINE Assunto principal: Febre do Nilo Ocidental / Vírus do Nilo Ocidental / Proteínas não Estruturais Virais / Receptores de IgG / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2006 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND / 4_TD Base de dados: MEDLINE Assunto principal: Febre do Nilo Ocidental / Vírus do Nilo Ocidental / Proteínas não Estruturais Virais / Receptores de IgG / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2006 Tipo de documento: Article