Abstract：
Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.
摘要：
麻疹病毒（MeV）是一种公共卫生威胁，随着普通人群的疫苗覆盖率下降和免疫功能低下的人群，这种威胁正在升级。谁不能接种疫苗，增加。没有批准的MeV疗法。靶向病毒融合的中和抗体是一种潜在的治疗方法，但尚未在结构上进行表征或推进临床使用。我们仅展示了预融合F的低温电子显微镜（cryo-EM）结构[2.1埃（µ）分辨率]，F与融合抑制肽（2.3-µ分辨率）复合，F与中和和保护性单克隆抗体（mAb）77（2.6-µ分辨率）复合，以及融合后F的附加结构（2.7-µ分辨率）。体外测定和其他EM类别的检查表明，mAb77结合融合前F，在中间状态逮捕F,并防止向融合后构象的过渡。这些结构揭示了抗体介导的中和，涉及将融合蛋白停滞在中间状态。
