Structure of human Aichi virus and implications for receptor binding
Structure of human Aichi virus and implications for receptor binding
复制标题
人类爱知病毒的结构及其对受体结合的影响。
DOI：
10.1038/nmicrobiol.2016.150
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发表时间：
2016-11-01
影响因子：
28.3
通讯作者：
Stuart, David I.
中科院分区：
文献类型：
--
作者：
Zhu, Ling;Wang, Xiangxi;Stuart, David I.
爱知病毒(AIV)是一种罕见且特征不佳的微小核糖核酸病毒，被归类为KobuVirus，可导致5岁以下儿童严重的胃肠炎和死亡，特别是在发展中国家(1，2)。在10岁以下的儿童中，AIV的血清阳性率约为60%，在以后的生活中(3，4)达到90%。目前还没有可用的疫苗或有效的抗病毒治疗。这里，我们描述了3.7埃的AIV的结构。这种柯布病毒的第一个高分辨率结构介于肠道病毒和心脏病毒之间，有一个浅而窄的凹陷，边界是突出的VP0 CD环(连接β-桶的C和D链)，取代了被称为峡谷的凹陷，峡谷通常是肠道病毒受体附着的位置。VP0没有被裂解形成VP2和VP4，因此VP2的β-桶结构与衣壳内部独特的延伸结构相辅相成。在外表面，在VP1的C末端存在以前在小核糖核酸病毒中未见的多聚脯氨酸螺旋结构，该位置在其他一些小核糖核酸病毒中发现了整合素结合基序。与此多聚氨酸基序相对应的多肽在一定程度上可以减弱病毒的感染性，可能会阻止宿主细胞的附着。这可能会指导细胞受体的识别。
Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries(1,2). The seroprevalence of AiV is approximately 60% in children under the age of ten years and reaches 90% later in life(3,4). There is no available vaccine or effective antiviral treatment. Here, we describe the structure of AiV at 3.7 angstrom. This first high-resolution structure for a kobuvirus is intermediate between those of the enteroviruses and cardioviruses, with a shallow, narrow depression bounded by the prominent VP0 CD loops (linking the C and D strands of the beta-barrel), replacing the depression known as the canyon, frequently the site of receptor attachment in enteroviruses. VP0 is not cleaved to form VP2 and VP4, so the 'VP2' beta-barrel structure is complemented with a unique extended structure on the inside of the capsid. On the outer surface, a polyproline helix structure, not seen previously in picornaviruses is present at the C terminus of VP1, a position where integrin binding motifs are found in some other picornaviruses. A peptide corresponding to this polyproline motif somewhat attenuates virus infectivity, presumably blocking host-cell attachment. This may guide cellular receptor identification.