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Cellular receptors for enterovirus A71
Journal of Biomedical Science ( IF 9.0 ) Pub Date : 2020-01-10 , DOI: 10.1186/s12929-020-0615-9
Kyousuke Kobayashi , Satoshi Koike

Enterovirus 71 (EV-A71) is one of the major causative agents of hand, foot, and mouth disease. EV-A71 infection is sometimes associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. Therefore, EV-A71 is a serious public health concern. Scavenger receptor class B, member 2 (SCARB2) is a type III transmembrane protein that belongs to the CD36 family and is a major receptor for EV-A71. SCARB2 supports attachment and internalization of the virus and initiates conformational changes that lead to uncoating of viral RNA in the cytoplasm. The three-dimensional structure of the virus-receptor complex was elucidated by cryo-electron microscopy. Two α-helices in the head domain of SCARB2 bind to the G-H loop of VP1 and the E-F loop of VP2 capsid proteins of EV-A71. Uncoating takes place in a SCARB2- and low pH-dependent manner. In addition to SCARB2, other molecules support cell surface binding of EV-A71. Heparan sulfate proteoglycans, P-selectin glycoprotein ligand-1, sialylated glycan, annexin II, vimentin, fibronectin, and prohibitin enhance viral infection by retaining the virus on the cell surface. These molecules are known as “attachment receptors” because they cannot initiate uncoating. In vivo, SCARB2 expression was observed in EV-A71 antigen-positive neurons and epithelial cells in the crypts of the palatine tonsils in patients that died of EV-A71 infection. Adult mice are not susceptible to infection by EV-A71, but transgenic mice that express human SCARB2 become susceptible to EV-A71 infection and develop neurological diseases similar to those observed in humans. Attachment receptors may also be involved in EV-A71 infection in vivo. Although heparan sulfate proteoglycans are expressed by many cultured cell lines and enhance infection by a subset of EV-A71 strains, they are not expressed by cells that express SCARB2 at high levels in vivo. Thus, heparan sulfate-positive cells merely adsorb the virus and do not contribute to replication or dissemination of the virus in vivo. In addition to these attachment receptors, cyclophilin A and human tryptophanyl aminoacyl-tRNA synthetase act as an uncoating regulator and an entry mediator that can confer susceptibility to non-susceptibile cells in the absence of SCARB2, respectively. The roles of attachment receptors and other molecules in EV-A71 pathogenesis remain to be elucidated.

中文翻译:

肠道病毒A71的细胞受体

肠病毒71(EV-A71)是手足口病的主要病原体之一。EV-A71感染有时与严重的神经系统疾病(例如急性脑炎,急性弛缓性麻痹和心肺功能衰竭)相关。因此,EV-A71是严重的公共卫生问题。B类清道夫受体成员2(SCARB2)是属于CD36家族的III型跨膜蛋白,是EV-A71的主要受体。SCARB2支持病毒的附着和内在化,并引发构象变化,从而导致细胞质中的病毒RNA脱壳。病毒受体复合物的三维结构通过冷冻电子显微镜得以阐明。SCARB2头部结构域中的两个α螺旋与VP1的GH环和EV-A71的VP2衣壳蛋白的EF环结合。脱膜以SCARB2和低pH依赖性方式进行。除SCARB2外,其他分子也支持EV-A71的细胞表面结合。硫酸乙酰肝素蛋白聚糖,P-选择蛋白糖蛋白配体-1,唾液酸化聚糖,膜联蛋白II,波形蛋白,纤连蛋白和禁止素通过将病毒保留在细胞表面来增强病毒感染。这些分子被称为“附着受体”,因为它们无法引发脱膜。在体内,在死于EV-A71感染的患者中,在tons扁桃体隐窝的EV-A71抗原阳性神经元和上皮细胞中观察到SCARB2表达。成年小鼠不易受EV-A71感染,但表达人SCARB2的转基因小鼠易受EV-A71感染,并发展出与人类所观察到的相似的神经系统疾病。附着受体也可能在体内参与EV-A71感染。尽管硫酸乙酰肝素蛋白聚糖在许多培养的细胞系中表达并增强了一部分EV-A71菌株的感染,但在体内高水平表达SCARB2的细胞中却不表达。因此,硫酸乙酰肝素阳性细胞仅吸收病毒,而无助于病毒在体内的复制或传播。除这些附着受体外,亲环蛋白A和人色氨酸氨酰基-tRNA合成酶还充当脱膜调节剂和进入介体,可分别在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。尽管硫酸乙酰肝素蛋白聚糖在许多培养的细胞系中表达并增强了一部分EV-A71菌株的感染,但在体内高水平表达SCARB2的细胞中却不表达。因此,硫酸乙酰肝素阳性细胞仅吸收病毒,而无助于病毒在体内的复制或传播。除这些附着受体外,亲环蛋白A和人色氨酸氨酰基-tRNA合成酶还充当脱膜调节剂和进入介体,可分别在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。尽管硫酸乙酰肝素蛋白聚糖在许多培养的细胞系中表达并增强了一部分EV-A71菌株的感染,但在体内高水平表达SCARB2的细胞中却不表达。因此,硫酸乙酰肝素阳性细胞仅吸收病毒,而无助于病毒在体内的复制或传播。除这些附着受体外,亲环蛋白A和人色氨酸氨酰基-tRNA合成酶还充当脱膜调节剂和进入介体,可分别在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。它们在体内不能以高水平表达SCARB2的细胞表达。因此,硫酸乙酰肝素阳性细胞仅吸收病毒,而无助于病毒在体内的复制或传播。除这些附着受体外,亲环蛋白A和人色氨酸氨酰基-tRNA合成酶还充当脱膜调节剂和进入介体,可分别在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。它们在体内不以高水平表达SCARB2的细胞表达。因此,硫酸乙酰肝素阳性细胞仅吸收病毒,而无助于病毒在体内的复制或传播。除这些附着受体外,亲环蛋白A和人色氨酸氨酰基-tRNA合成酶还充当脱膜调节剂和进入介体,可分别在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。亲环蛋白A和人色氨酸氨酰-tRNA合成酶分别充当脱膜调节剂和进入介体,可在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。亲环蛋白A和人色氨酸氨酰-tRNA合成酶分别充当脱膜调节剂和进入介体,可在不存在SCARB2的情况下赋予非易感细胞敏感性。附着受体和其他分子在EV-A71发病机理中的作用仍有待阐明。
更新日期:2020-04-07
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