Potent neutralization of Hepatitis A virus reveals a receptor mimic mechanism
讲座名称：
Potent neutralization of Hepatitis A virus reveals a receptor mimic mechanism
讲座时间：
2016-07-12
讲座人：
王祥喜
形式：
校区：
兴庆校区
实践学分：
讲座内容：
报告题目：Potent neutralization of Hepatitis A virus reveals a receptor mimic mechanism
报 告 人：王祥喜 博士，中科院生物物理研究所，研究员
报告时间：2016年7月12日（星期二）上午10:30-11:15
报告地点：中一楼3113
报告摘 要：
Hepatitis A virus (HAV) infects ~1.4 million people annually and whilst there is a vaccine, there are no licensed therapeutic drugs. Hepatoviruses are unusual among picornaviruses, both in targeting the liver and also in their structure and life cycle. Here we show that nM concentrations of HAV-specific monoclonal antibody R10 neutralize virus infection efficiently. Cryo-EM structures of HAV full particles and empty particles at 3.4 Å and 3.8 Å resolution reveal a ‘layered’ RNA genome and altered inner capsid layer distinguishing the full and empty particles. The cryo-EM structure of full particles complexed with R10 Fab at 4.2 Å resolution, together with the crystal structure of R10 Fab allowed us to build a reliable model of the complex. R10 binds across the pentamer interface interfering with receptor attachment and viral uncoating, shedding light on the hitherto unknown mechanism by which this extraordinarily stable virus releases its RNA and demonstrating new opportunities for therapeutic intervention.
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