【前沿速递】饶子和院士团队,《PNAS》报道发现一甲型肝炎病毒特异性中和抗体
甲型肝炎病毒（HAV）仍然是神秘的，物理上异常稳定。 其中受体结合以及如何可以使病毒体不稳定以释放基因组是未知的。
中科院生物物理研究所、清华大学医学院的饶子和院士、牛津大学的David I. Stuart、Elizabeth E. Fry以及中科院生物物理研究所的Xiangxi Wang组成的团队，在《PNAS》2017年1月10日最新报道，发现了一个可以有效的阻断受体附着和干扰病毒去膜的HAV特异性中和单克隆抗体——R10。
Fig.2 HAV全粒子、空粒子结构图
Fig.3 R10结合在HAV表面的冷冻电镜结构
这项研究确定了HAV全粒子，空粒子和与R10 Fab复合的全粒子的高分辨率低温EM结构，揭示了R10沿着病毒的五聚体结构块的边缘结合到病毒表面，并且这些相互作用 对于受体结合和病毒脱壳是关键的。 同时这项研究结果指向使用受体模拟机制中和病毒感染，强调治疗干预的新机会。
Title:Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site
doi: 10.1073/pnas.1616502114
Abstract:
Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.
Significance:
Hepatitis A virus (HAV) remains enigmatic, being unusually stable physically. Where the receptor binds and how the virion can be destabilized to release the genome are unknown. We report a potent HAV-specific neutralizing monoclonal antibody, R10, that blocks receptor attachment and interferes with viral uncoating. We have determined high-resolution cryo-EM structures of HAV full particles, empty particles, and full particles complexed with R10 Fab, revealing that R10 binds to the viral surface along the edges of the pentameric building block of the virus, and these interactions are critical for receptor binding and viral uncoating. Our results point to the use of a receptor mimic mechanism to neutralize virus infection, highlighting new opportunities for therapeutic intervention.
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