title: Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization.
abstract: West Nile virions incorporate 180 envelope (E) proteins that orchestrate the process of virus entry and are the primary target of neutralizing antibodies. The E proteins of newly synthesized West Nile virus (WNV) are organized into trimeric spikes composed of pre-membrane (prM) and E protein heterodimers. During egress, immature virions undergo a protease-mediated cleavage of prM that results in a reorganization of E protein into the pseudo-icosahedral arrangement characteristic of mature virions. While cleavage of prM is a required step in the virus life cycle, complete maturation is not required for infectivity and infectious virions may be heterogeneous with respect to the extent of prM cleavage. In this study, we demonstrate that virion maturation impacts the sensitivity of WNV to antibody-mediated neutralization. Complete maturation results in a significant reduction in sensitivity to neutralization by antibodies specific for poorly accessible epitopes that comprise a major component of the human antibody response following WNV infection or vaccination. This reduction in neutralization sensitivity reflects a decrease in the accessibility of epitopes on virions to levels that fall below a threshold required for neutralization. Thus, in addition to a role in facilitating viral entry, changes in E protein arrangement associated with maturation modulate neutralization sensitivity and introduce an additional layer of complexity into humoral immunity against WNV.
authors.affiliation: Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Steevenson
authors.initials: S
authors.lastname: Nelson
authors.forename: Christiane A
authors.initials: CA
authors.lastname: Jost
authors.forename: Qinq
authors.initials: Q
authors.lastname: Xu
authors.forename: Jessica
authors.initials: J
authors.lastname: Ess
authors.forename: Julie E
authors.initials: JE
authors.lastname: Martin
authors.forename: Theodore
authors.initials: T
authors.lastname: Oliphant
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D017321:Clinical Trials, Phase I as Topic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D009500:Neutralization Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000378:metabolism; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000254:growth & development / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014759:Viral Envelope Proteins