Novel Naturally Occurring Mutations of Enterovirus 71 Associated With Disease Severity.
Novel Naturally Occurring Mutations of Enterovirus 71 Associated With Disease Severity.
复制标题
DOI：
10.3389/fmicb.2020.610568
复制
发表时间：
2020
影响因子：
5.2
通讯作者：
Shih C
中科院分区：
文献类型：
--
作者：
Chang CS;Liao CC;Liou AT;Chou YC;Yu YY;Lin CY;Lin JS;Suen CS;Hwang MJ;Shih C
感染重新出现的肠道病毒71型(EV-A71)与一系列疾病的严重程度有关，包括疱疹心绞痛、脑炎和心肺衰竭。目前，还没有FDA批准的治疗EV-A71的药物。高危儿童的早期诊断是成功救治的关键。我们检测了36例轻症和27例重症患者的病毒基因组5‘非翻译区和衣壳蛋白VP1的序列。我们发现了5个与严重疾病相关的EV-A71突变，包括(1)5‘非编码区C580U、A707G、C709U突变；(2)280位(280T)VP1丙氨酸到苏氨酸突变；(3)145位VP1谷氨酸到(非谷氨酸)突变[145(非E)]。SCARB2是已知的EV-A71进入受体。根据最近EV-A71-SCARB2结合复合体的低温EM结构，VP1-280T位于VP1-VP2复合体与其进入受体SCARB2之间的结合界面附近。从头开始在突变的VP1-280T和VP2-139T之间产生氢键，有助于加强VP1-VP2复合体的网状相互作用结构。VP2的稳定环路一旦与SCARB2接触，就可以增强与宿主SCARB2受体的相互作用，从而使病毒进入。我们的研究结果有助于临床早期发现感染EV-A71的重症病例。此外，它还为未来通过感染性的cDNA克隆、定点突变和动物模型进行功能研究开辟了机会。
Infection with the re-emerging enterovirus 71 (EV-A71) is associated with a wide range of disease severity, including herpangina, encephalitis, and cardiopulmonary failure. At present, there is no FDA-approved therapeutics for EV-A71. Early diagnosis for the high-risk children is the key to successful patient care. We examined viral genome sequences at the 5′ untranslated region (UTR) and the capsid protein VP1 from 36 mild and 27 severe cases. We identified five EV-A71 mutations associated with severe diseases, including (1) the 5′ UTR mutations C580U, A707G, C709U; (2) a VP1 alanine-to-threonine mutation at position 280 (280T), and (3) a VP1 glutamic acid-to-(non-glutamic acid) at position 145 [145(non-E)]. SCARB2 is a known entry receptor for EV-A71. Based on a recent cryoEM structure of the EV-A71-SCARB2 binding complex, VP1-280T is near the binding interface between the VP1-VP2 complex and its entry receptor SCARB2. A de novo created hydrogen bonding between the mutant VP1-280T and the VP2-139T, could help strengthen a web-like interaction structure of the VP1-VP2 complex. A stabilized loop turn of VP2, once in contact with SCARB2, can enhance interaction with the host SCARB2 receptor for viral entry. Our findings here could facilitate early detection of severe cases infected with EV-A71 in clinical medicine. In addition, it opens up the opportunity of functional studies via infectious cDNA cloning, site-directed mutagenesis, and animal models in the future.
登录
查看更多内容
影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
6.7
作者：
Kataoka C;Suzuki T;Kotani O;Iwata-Yoshikawa N;Nagata N;Ami Y;Wakita T;Nishimura Y;Shimizu H
通讯作者：
Shimizu H
影响因子：
5
作者：
Chang, Guo-hui;Lin, Lei;Zhu, Qing-yu
通讯作者：
Zhu, Qing-yu
影响因子：
4.8
作者：
Chen, Pan;Song, Zilin;Li, Wenhui
通讯作者：
Li, Wenhui
影响因子：
6.7
作者：
Cordey S;Petty TJ;Schibler M;Martinez Y;Gerlach D;van Belle S;Turin L;Zdobnov E;Kaiser L;Tapparel C
通讯作者：
Tapparel C