登革热病毒病毒. 抗体的冷EM结构通过锁定E蛋白二分体来中和2型登革热病毒
Guntur Fibriansah1, Kristie D Ibarra2, Thiam-Seng Ng1
1Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
Science (New York, N.Y.)
|July 4, 2015
概括
一种新的人类单克隆抗体,2D22通过向DENV血清型2来显示对抗严重登革热病毒感染的治疗潜力. 化EM结构揭示了这种抗体如何中和病毒,为新的登革热疫苗和治疗提供了潜在的目标.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 登革热病毒 (DENV) 有四种血清型,而先前感染可以增强其他血清型的后续感染.
- 抗体依赖增强 (ADE) 对登革热疗法和疫苗构成了挑战.
研究的目的:
- 为了研究DENV血清型2特定的人类单克隆抗体 (HMAb) 2D22.22的治疗潜力.
- 阐明HMAb 2D22对DENV2.2的中和机制的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定HMAb 2D22的结构,并与两个DENV2菌株复合.
- 用一种抗体增强严重登革热病的小鼠模型来评估治疗疗效.
主要成果:
- HMAb 2D22在抗体增强严重登革热的小鼠模型中显示出治疗效果.
- 低温-EM结构显示,HMAb 2D22在二维结构中的DENV2包膜 (E) 蛋白中结合.
- 这种结合可能会抑制病毒融合所必需的E蛋白重组,有效地"锁定"病毒二极体.
结论:
- HMAb 2D22是抗体增强的严重登革热病的有希望的治疗候选者.
- 被HMAb 2D22准的已识别的表位是开发新型登革热疫苗和治疗方法的潜在目标.
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