Xiaojing Lin, Jianhong Gan, Qiang Sun, Zi Li, Kun Qin, Yong Zhang, Yang Cao, Jianfang Zhou
{"title":"肠道病毒 VP1 袋的结构框架和开口外观与病毒的耐热性相关。","authors":"Xiaojing Lin, Jianhong Gan, Qiang Sun, Zi Li, Kun Qin, Yong Zhang, Yang Cao, Jianfang Zhou","doi":"10.3390/pathogens13080711","DOIUrl":null,"url":null,"abstract":"<p><p>Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket in EVs is poor. Here, we compared the published capsid crystals of EVs and RVs and proposed a structural framework for the VP1-pocket: Frame 1-4, which is located at the CD loop, GH loop, and C-terminus, presenting with an outward opening appearance or not. The non-outward viral strains-CVB3, Echo 11, RV-A81, and RV-B70-are more thermally stable, with a breakpoint temperature (B.T.) of 51~62 °C for genome releasing, which is 4~10 °C higher than its outward temperature of 41~47 °C, and infectivity preservation when treated at 50 °C for 3 min. Its outward versus non-outward opening is correlated significantly with the B.T. for genome release (<i>r</i> = -0.90; <i>p</i> = 0.0004) and infectivity (<i>r</i> = -0.82, <i>p</i> = 0.0039). The energy of Frames 1, 2, and 4, including <i>Van der Waals</i> attractive and repulsive interactions and hydrogen bonds, showed significant correlations with the B.T. (r = -0.67, 0.75, and -0.8; <i>p</i> = 0.034, 0.013, and 0.006, respectively). These characters of the VP1-pocket could be predictors for virion thermostability and aid in the development of vaccines or antivirals.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357065/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Structural Framework and Opening Appearance of the VP1-Pocket of Enteroviruses Correlated with Viral Thermostability.\",\"authors\":\"Xiaojing Lin, Jianhong Gan, Qiang Sun, Zi Li, Kun Qin, Yong Zhang, Yang Cao, Jianfang Zhou\",\"doi\":\"10.3390/pathogens13080711\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket in EVs is poor. Here, we compared the published capsid crystals of EVs and RVs and proposed a structural framework for the VP1-pocket: Frame 1-4, which is located at the CD loop, GH loop, and C-terminus, presenting with an outward opening appearance or not. The non-outward viral strains-CVB3, Echo 11, RV-A81, and RV-B70-are more thermally stable, with a breakpoint temperature (B.T.) of 51~62 °C for genome releasing, which is 4~10 °C higher than its outward temperature of 41~47 °C, and infectivity preservation when treated at 50 °C for 3 min. Its outward versus non-outward opening is correlated significantly with the B.T. for genome release (<i>r</i> = -0.90; <i>p</i> = 0.0004) and infectivity (<i>r</i> = -0.82, <i>p</i> = 0.0039). The energy of Frames 1, 2, and 4, including <i>Van der Waals</i> attractive and repulsive interactions and hydrogen bonds, showed significant correlations with the B.T. (r = -0.67, 0.75, and -0.8; <i>p</i> = 0.034, 0.013, and 0.006, respectively). These characters of the VP1-pocket could be predictors for virion thermostability and aid in the development of vaccines or antivirals.</p>\",\"PeriodicalId\":19758,\"journal\":{\"name\":\"Pathogens\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357065/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pathogens\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/pathogens13080711\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathogens","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/pathogens13080711","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
The Structural Framework and Opening Appearance of the VP1-Pocket of Enteroviruses Correlated with Viral Thermostability.
Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket in EVs is poor. Here, we compared the published capsid crystals of EVs and RVs and proposed a structural framework for the VP1-pocket: Frame 1-4, which is located at the CD loop, GH loop, and C-terminus, presenting with an outward opening appearance or not. The non-outward viral strains-CVB3, Echo 11, RV-A81, and RV-B70-are more thermally stable, with a breakpoint temperature (B.T.) of 51~62 °C for genome releasing, which is 4~10 °C higher than its outward temperature of 41~47 °C, and infectivity preservation when treated at 50 °C for 3 min. Its outward versus non-outward opening is correlated significantly with the B.T. for genome release (r = -0.90; p = 0.0004) and infectivity (r = -0.82, p = 0.0039). The energy of Frames 1, 2, and 4, including Van der Waals attractive and repulsive interactions and hydrogen bonds, showed significant correlations with the B.T. (r = -0.67, 0.75, and -0.8; p = 0.034, 0.013, and 0.006, respectively). These characters of the VP1-pocket could be predictors for virion thermostability and aid in the development of vaccines or antivirals.
期刊介绍:
Pathogens (ISSN 2076-0817) publishes reviews, regular research papers and short notes on all aspects of pathogens and pathogen-host interactions. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental and/or methodical details must be provided for research articles.