近日，北京生命科学研究所李文辉实验室在Journal of Biological Chemistry杂志发表题为“Molecular Determinants of Enterovirus 71 Viral Entry： Cleft around Gln-172 on VP1 protein interacts with Variable region on Scavenge Receptor B2”的论文。文章中，研究者揭示了EV71病毒的感染过程及建立了一种EV71单轮感染假病毒报告系统。
近年来，手足口病（Hand-Foot-and-Mouth Disease， HFMD）在我国相当一部分地区流行，该病2011年报告发病数居丙类传染病第一位，严重威胁婴幼儿健康。肠道病毒71型(Enterovirus 71， EV71)是引起手足口病的主要病原体之一。深入研究该病毒侵入细胞的过程对于理解病毒的致病机制，发展有针对性的预防及治疗手段有重要意义。
李文辉实验室通过系统研究发现EV71病毒通过其表面壳蛋白（VP1）五聚体周围的“峡谷” 区与已知的细胞受体（SCARB2）分子结合，病毒与SCARB2的结合使病毒粒子构象发生变化，这种变化(160S->135S)在病毒被内吞(内体pH 降低)过程中显著增加而使病毒衣壳不稳定，最终导致病毒粒子释放病毒基因组RNA完成感染过程。研究过程中还建立了一种新颖的EV71单轮感染假病毒报告系统（single-round pseudotype reporter system），这一系统具有高灵敏和高可靠性，并能快速定量，为EV71侵入细胞分子机理的基础研究，EV71血清流行病学调查与疫苗中和抗体评价，以及筛选抗EV71感染抑制剂等工作提供了新的有价值的技术手段。
我所和协和医学院联合培养博士研究生陈盼，技术员宋子林和祁永和为本文的共同第一作者，李文辉博士为本文的通讯作者。该项研究由科技部973项目和北京市科委资助。（生物谷Bioon.com）
doi:10.1074/jbc.M111.301622
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Molecular Determinants of Enterovirus 71 Viral Entry CLEFT AROUND GLN-172 ON VP1 PROTEIN INTERACTS WITH VARIABLE REGION ON SCAVENGE RECEPTOR B 2
Pan Chen‡§,1, Zilin Song§,1, Yonghe Qi§,1, Xiaofeng Feng§, Naiqing Xu§, Yinyan Sun§, Xing Wu¶, Xin Yao¶, Qunyin Mao¶, Xiuling Li‖, Wenjuan Dong§, Xiaobo Wan§, Niu Huang§, Xinliang Shen‖, Zhenglun Liang¶ and Wenhui Li§,2
Enterovirus 71 (EV71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the Asia-Pacific region in recent years. Human scavenger receptor class B 2 (SCARB2) is the main cellular receptor for EV71 on target cells. The requirements of the EV71-SCARB2 interaction have not been fully characterized, and it has not been determined whether SCARB2 serves as an uncoating receptor for EV71. Here we compared the efficiency of the receptor from different species including human, horseshoe bat, mouse, and hamster and demonstrated that the residues between 144 and 151 are critical for SCARB2 binding to viral capsid protein VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. We also identified that EV71 binds to SCARB2 via a canyon of VP1 around residue Gln-172. Soluble SCARB2 could convert the EV71 virions from 160 S to 135 S particles, indicating that SCARB2 is an uncoating receptor of the virus. The uncoating efficiency of SCARB2 significantly increased in an acidic environment (pH 5.6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions.
