Maturation of west nile virus modulates sensitivity to antibody-mediated neutralization

被引:142
作者
Nelson, Steevenson [1 ]
Jost, Christiane A. [1 ]
Xu, Qinq [1 ]
Ess, Jessica [1 ]
Martin, Julie E. [2 ]
Oliphant, Theodore [3 ,4 ,5 ]
Whitehead, Stephen S. [6 ]
Durbin, Anna P. [7 ]
Graham, Barney S. [2 ]
Diamond, Michael S. [3 ,4 ,5 ]
Pierson, Theodore C. [1 ]
机构
[1] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA
[2] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA
[3] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
[6] NIH, Infect Dis Lab, Bethesda, MD 20892 USA
[7] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA
关键词
D O I
10.1371/journal.ppat.1000060
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:10
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