近日，北京生命科學(xué)研究所李文輝實驗室在Journal of Biological Chemistry雜志發(fā)表題為“Molecular Determinants of Enterovirus 71 Viral Entry： Cleft around Gln-172 on VP1 protein interacts with Variable region on Scavenge Receptor B2”的論文,。文章中,，研究者揭示了EV71病毒的感染過程及建立了一種EV71單輪感染假病毒報告系統(tǒng)。
近年來,，手足口?。℉and-Foot-and-Mouth Disease， HFMD）在我國相當(dāng)一部分地區(qū)流行,，該病2011年報告發(fā)病數(shù)居丙類傳染病第一位,，嚴(yán)重威脅嬰幼兒健康。腸道病毒71型(Enterovirus 71,， EV71)是引起手足口病的主要病原體之一,。深入研究該病毒侵入細(xì)胞的過程對于理解病毒的致病機(jī)制，發(fā)展有針對性的預(yù)防及治療手段有重要意義,。
李文輝實驗室通過系統(tǒng)研究發(fā)現(xiàn)EV71病毒通過其表面殼蛋白（VP1）五聚體周圍的“峽谷” 區(qū)與已知的細(xì)胞受體（SCARB2）分子結(jié)合,，病毒與SCARB2的結(jié)合使病毒粒子構(gòu)象發(fā)生變化，這種變化(160S->135S)在病毒被內(nèi)吞(內(nèi)體pH 降低)過程中顯著增加而使病毒衣殼不穩(wěn)定,，最終導(dǎo)致病毒粒子釋放病毒基因組RNA完成感染過程,。研究過程中還建立了一種新穎的EV71單輪感染假病毒報告系統(tǒng)（single-round pseudotype reporter system），這一系統(tǒng)具有高靈敏和高可靠性,，并能快速定量,，為EV71侵入細(xì)胞分子機(jī)理的基礎(chǔ)研究，EV71血清流行病學(xué)調(diào)查與疫苗中和抗體評價,，以及篩選抗EV71感染抑制劑等工作提供了新的有價值的技術(shù)手段,。
我所和協(xié)和醫(yī)學(xué)院聯(lián)合培養(yǎng)博士研究生陳盼，技術(shù)員宋子林和祁永和為本文的共同第一作者,，李文輝博士為本文的通訊作者。該項研究由科技部973項目和北京市科委資助,。（生物谷Bioon.com）
doi:10.1074/jbc.M111.301622
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PMID:
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.
