Molecular Determinants of Enterovirus 71 Viral Entry CLEFT AROUND GLN-172 ON VP1 PROTEIN INTERACTS WITH VARIABLE REGION ON SCAVENGE RECEPTOR B 2
Molecular Determinants of Enterovirus 71 Viral Entry CLEFT AROUND GLN-172 ON VP1 PROTEIN INTERACTS WITH VARIABLE REGION ON SCAVENGE RECEPTOR B 2
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DOI：
10.1074/jbc.m111.301622
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发表时间：
2012-02-24
影响因子：
4.8
通讯作者：
Li, Wenhui
中科院分区：
文献类型：
--
作者：
Chen, Pan;Song, Zilin;Li, Wenhui
肠病毒71型（EV71）是近年来引起亚太地区幼儿手足口病暴发的主要病原体之一。人清道夫受体b2 （SCARB2）是EV71在靶细胞上的主要细胞受体。EV71-SCARB2相互作用的要求尚未被完全表征，也尚未确定SCARB2是否作为EV71的剥膜受体。在这里，我们比较了不同物种（包括人、马蹄蝠、小鼠和仓鼠）的SCARB2受体的效率，并证明144和151之间的残基是SCARB2与EV71病毒衣壳蛋白VP1结合的关键，而来自人类受体的7个残基可以将小鼠的SCARB2（一个低效的受体）转化为EV71病毒感染的高效受体。我们还发现EV71通过残基Gln-172周围的VP1峡谷与SCARB2结合。可溶性SCARB2可将EV71病毒粒子从160 S转化为135 S，表明SCARB2是病毒的剥膜受体。在酸性环境（pH 5.6）下，SCARB2的剥膜效率显著提高。这些研究阐明了肠病毒71型感染的病毒衣壳和受体决定因素，并揭示了抗病毒干预的可能靶点。
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.