人类H3N2流感病毒受体特异性的演变已经大大扩大了受体结合域网站
Andrew J Thompson1, Nicholas C Wu2, Angeles Canales3
1Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell host & microbe
|February 2, 2024
概括
人类流感H3N2病毒进化以结合复杂的人类细胞受体,影响抗原变异和疫苗不匹配. 这种适应对于理解流感传播和演变至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 人类流感病毒,如H3N2,是从鸟类祖先进化而来的.
- 禽流感病毒与α2-3结合的酸结合,而人类菌株必须适应人类呼吸道细胞上的α2-6结合的酸,以有效传播.
- 自1968年大流行以来,H3N2亚型经历了显著的演变.
研究的目的:
- 为了研究H3N2血凝素 (HA) 对人类呼吸道糖的进化适应.
- 了解H3N2病毒如何在过去的五十年里进化以识别复杂的人类化物受体.
- 阐明改变受体参与的结构基础及其对抗原漂移的影响.
主要方法:
- 分析H3N2血凝素的演变和受体结合.
- 糖甘结合测试以评估与不同酸盐的相互作用.
- 对血凝素trimers的结构分析,以确定受体结合部位和表面残留物的变化.
- 受体参与表型与抗原位点演变的相关性.
主要成果:
- H3N2病毒逐渐进化,以优先结合延长的α2-6-sialoside受体,这些受体在人类呼吸道中丰富.
- 最近的H3N2菌株与这些延长的受体呈现出越来越复杂的相互作用.
- HA的受体结合部位已经扩大到包括抗原部位中的残留物,促进了对这些复杂的甘氨酸的识别.
- 这种适应解释了当H3N2病毒在缺乏这些特定受体的环境中传播时,抗原变异的选择,例如蛋.
结论:
- H3N2血凝素已经经历了对人类特异性酸链接和糖结构的显著适应.
- 在H3N2中,受体结合的演变与抗原部位的变化有关,这有助于抗原漂移和疫苗不匹配.
- 了解这些进化动态对于预测流感病毒行为和提高疫苗疗效至关重要.
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