Scavenger receptor B2 is a cellular receptor for enterovirus 71

Scavenger receptor B2 is a cellular receptor for enterovirus 71
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DOI:
10.1038/nm.1992
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发表时间:
2009-07-01
期刊:
影响因子:
82.9
通讯作者:
Koike, Satoshi
Koike, Satoshi
中科院分区:
医学1区
文献类型:
--
作者:
Yamayoshi, Seiya;Yamashita, Yasuko;Koike, Satoshi

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肠病毒71型(EV71)属于小核糖核酸病毒科肠病毒属人类肠道病毒A种(1)。EV71和柯萨奇病毒A16 (CVA16)最常与手足口病(HFMD)相关(1)。虽然手足口病被认为是一种轻微的疹性感染,但涉及EV71而非CVA16的感染可发展为严重的神经系统疾病,包括致命性脑炎、无菌性脑膜炎和急性弛缓性麻痹(2)。近年来,在台湾、马来西亚、新加坡、日本和中国报告了神经毒性EV71感染的流行和散发暴发(3-7)。在这里,我们发现人类清净受体B类成员2 (SCARB2,也称为溶酶体整体膜蛋白II或CD36b样-2)是EV71的受体。EV71结合可溶性SCARB2或表达SCARB2的细胞,并被SCARB2抗体抑制。人SCARB2的表达使正常情况下不敏感的细胞系支持EV71的繁殖并产生细胞病变效应。EV71感染受到SCARB2抗体和可溶性SCARB2抗体的抑制。SCARB2也支持较温和的病原体CVA16的感染。SCARB2作为EV71和CVA16受体的鉴定有助于更好地了解这些病毒的致病性。
Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae(1). EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD)(1). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis(2). In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China(3-7). Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.