首页 > 最新文献

Virus research最新文献

英文 中文
Engineering a robust infectious clone and gene silencing vector from blackberry yellow vein associated virus. 从黑莓黄脉相关病毒中提取强感染性克隆和基因沉默载体。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.virusres.2024.199488
Andrea Sierra Mejia, Dan E V Villamor, Aaron Rocha, William M Wintermantel, Ioannis E Tzanetakis

Criniviruses are emerging pathogens responsible for significant disease outbreaks worldwide. Among them, blackberry yellow vein-associated virus (BYVaV) is prevalent in blackberry-producing areas of the United States and, when present in the blackberry yellow vein disease complex with other viruses, can lead to substantial crop losses. To better understand BYVaV biology and its role in virus complex disease development, we developed a BYVaV-derived infectious clone and a virus-induced gene silencing (VIGS) vector. The infectious clone successfully induced systemic infection and symptom development in Nicotiana benthamiana. Additionally, transmission of the recombinant virus to indicator plants was confirmed using the whitefly vector Trialeurodes vaporariorum. The infectious clone was subsequently modified into a VIGS vector, with the foreign insert remaining stable for the length of the study. This work provides essential tools for advancing the study of BYVaV biology and conducting genomic studies in its natural hosts.

Criniviruses 是一种新出现的病原体,在全球范围内造成了严重的疾病爆发。其中,黑莓黄脉相关病毒(BYVaV)在美国的黑莓产区很普遍,当它与其他病毒一起出现在黑莓黄脉病复合体中时,会导致作物遭受重大损失。为了更好地了解 BYVaV 的生物学特性及其在病毒复合体病害发展中的作用,我们开发了 BYVaV 衍生的感染性克隆和病毒诱导基因沉默(VIGS)载体。该感染性克隆成功诱导了烟草花的系统感染和症状发展。此外,利用粉虱载体 Trialeurodes vaporariorum 证实了重组病毒向指示植物的传播。感染性克隆随后被改造成 VIGS 载体,外来插入物在整个研究过程中保持稳定。这项工作为推进 BYVaV 生物学研究和在其自然宿主中开展基因组研究提供了重要工具。
{"title":"Engineering a robust infectious clone and gene silencing vector from blackberry yellow vein associated virus.","authors":"Andrea Sierra Mejia, Dan E V Villamor, Aaron Rocha, William M Wintermantel, Ioannis E Tzanetakis","doi":"10.1016/j.virusres.2024.199488","DOIUrl":"10.1016/j.virusres.2024.199488","url":null,"abstract":"<p><p>Criniviruses are emerging pathogens responsible for significant disease outbreaks worldwide. Among them, blackberry yellow vein-associated virus (BYVaV) is prevalent in blackberry-producing areas of the United States and, when present in the blackberry yellow vein disease complex with other viruses, can lead to substantial crop losses. To better understand BYVaV biology and its role in virus complex disease development, we developed a BYVaV-derived infectious clone and a virus-induced gene silencing (VIGS) vector. The infectious clone successfully induced systemic infection and symptom development in Nicotiana benthamiana. Additionally, transmission of the recombinant virus to indicator plants was confirmed using the whitefly vector Trialeurodes vaporariorum. The infectious clone was subsequently modified into a VIGS vector, with the foreign insert remaining stable for the length of the study. This work provides essential tools for advancing the study of BYVaV biology and conducting genomic studies in its natural hosts.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive phylogenomic analysis of Zika virus: Insights into its origin, past evolutionary dynamics, and global spread. 寨卡病毒的全面系统发生组分析:洞察寨卡病毒的起源、过去的进化动态和全球传播。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.virusres.2024.199490
Nicola Zadra, Annapaola Rizzoli

Background: Zika virus (ZIKV), a Flaviviridae family member, has been linked to severe neurological disorders. Despite detailed studies on recent outbreaks, the early evolutionary history of ZIKV remains partially unclear. This study elucidates ZIKV origin and evolutionary dynamics, focusing on recombination events, early lineage diversification, and virus spread across continents.

Methods: We assessed recombination using multiple methods. We conducted Bayesian phylogenetic analyses to understand the evolutionary relationships and timing of key diversification events. Model selection was carried out to determine the most appropriate evolutionary model for our dataset.

Results: Our phylogenies revealed recent recombination between Singaporean and African lineages, indicating the co-circulation of diverse lineages during outbreaks. Thailand was identified as a crucial hub in the spread across Asia. The phylogenetic analysis suggests that the ZIKV lineage dates back to the eleventh century, with the first significant diversification occurring in the nineteenth century. The timing of the re-introduction of the Asian lineage into Africa and the delay between probable introduction and outbreak onset were also determined.

Conclusions: This study provides novel insights into ZIKV's origin and early evolutionary dynamics, highlighting Thailand's role in the spread of the virus in Asia and recent recombination events between distant lineages. These findings emphasize the need for continuous surveillance and a better understanding of ZIKV biology to forecast and mitigate future outbreaks.

背景:寨卡病毒(ZIKV)是弗拉维病毒科的一种病毒,与严重的神经系统疾病有关。尽管对近期爆发的疫情进行了详细研究,但 ZIKV 的早期进化史仍部分不清楚。本研究阐明了ZIKV的起源和进化动态,重点关注重组事件、早期血统多样化和病毒跨洲传播:我们使用多种方法评估了重组。我们进行了贝叶斯系统发生学分析,以了解关键分化事件的进化关系和时间。我们进行了模型选择,以确定最适合我们数据集的进化模型:我们的系统发生学揭示了新加坡和非洲血统之间最近的重组,表明在疫情爆发期间,不同血统之间存在共同循环。泰国被认为是疫情在亚洲蔓延的关键枢纽。系统发生学分析表明,ZIKV 的血统可追溯到 11 世纪,第一次显著的多样化发生在 19 世纪。研究还确定了亚洲血统再次传入非洲的时间,以及可能的传入与疫情爆发之间的延迟时间:这项研究为 ZIKV 的起源和早期进化动态提供了新的见解,突出了泰国在病毒在亚洲传播过程中的作用,以及最近在遥远血统之间发生的重组事件。这些发现强调了持续监测和更好地了解 ZIKV 生物学特性的必要性,以预测和缓解未来的疫情爆发。
{"title":"Comprehensive phylogenomic analysis of Zika virus: Insights into its origin, past evolutionary dynamics, and global spread.","authors":"Nicola Zadra, Annapaola Rizzoli","doi":"10.1016/j.virusres.2024.199490","DOIUrl":"10.1016/j.virusres.2024.199490","url":null,"abstract":"<p><strong>Background: </strong>Zika virus (ZIKV), a Flaviviridae family member, has been linked to severe neurological disorders. Despite detailed studies on recent outbreaks, the early evolutionary history of ZIKV remains partially unclear. This study elucidates ZIKV origin and evolutionary dynamics, focusing on recombination events, early lineage diversification, and virus spread across continents.</p><p><strong>Methods: </strong>We assessed recombination using multiple methods. We conducted Bayesian phylogenetic analyses to understand the evolutionary relationships and timing of key diversification events. Model selection was carried out to determine the most appropriate evolutionary model for our dataset.</p><p><strong>Results: </strong>Our phylogenies revealed recent recombination between Singaporean and African lineages, indicating the co-circulation of diverse lineages during outbreaks. Thailand was identified as a crucial hub in the spread across Asia. The phylogenetic analysis suggests that the ZIKV lineage dates back to the eleventh century, with the first significant diversification occurring in the nineteenth century. The timing of the re-introduction of the Asian lineage into Africa and the delay between probable introduction and outbreak onset were also determined.</p><p><strong>Conclusions: </strong>This study provides novel insights into ZIKV's origin and early evolutionary dynamics, highlighting Thailand's role in the spread of the virus in Asia and recent recombination events between distant lineages. These findings emphasize the need for continuous surveillance and a better understanding of ZIKV biology to forecast and mitigate future outbreaks.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 transactivate HSV-1 ICP0 promoter sequences but a GC-rich binding antibiotic, Mithramycin A, impairs reactivation from latency 糖皮质激素受体和特异性蛋白 1(Sp1)或 Sp3 可反式激活 HSV-1 ICP0 启动子序列,但一种富含 GC 结合力的抗生素 Mithramycin A 会影响潜伏期的再激活。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-11-04 DOI: 10.1016/j.virusres.2024.199487
Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency. Furthermore, GR and Krüppel-like factor 15 (KLF15) cooperatively transactivate cis-regulatory modules (CRMs) that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. KLF and specificity protein (Sp) family members bind GC-rich or C-rich sequences and belong to the same super-family of transcription factors. Based on these observations, we hypothesized CRMs spanning the ICP0 promoter are transactivated by GR and Sp1 or Sp3. CRM-A (-800 to -635), CRM-B (-485 to -635), and CRM-D (-232 to -24), but not CRM-C, were significantly transactivated by GR, DEX, and Sp1 or Sp3 in mouse neuroblastoma cells (Neuro-2A). Mutagenesis of Sp1/Sp3 binding sites were important for transactivation of CRM-A and CRM-B. Chromatin immunoprecipitation studies revealed significantly higher levels of GR occupied ICP0 promoter sequences when Sp1 or Sp3 was over-expressed suggesting these transcriptions factors recruit GR to ICP0 CRM sequences. Mithramycin A, an antibiotic that preferentially binds GC-rich DNA and impairs Sp1/Sp3 dependent transactivation and reduced virus shedding during reactivation from latency in mice latently infected with HSV-1. These studies indicate GR and certain stress-induced cellular transcription factors preferentially bind GC rich DNA, which stimulates HSV-1 gene expression and reactivation from latency in trigeminal ganglia of latently infected mice.
糖皮质激素受体(GR)的激活会增强人类α-疱疹病毒1(HSV-1)的复制,并促使其从潜伏期重新活化。此外,GR 和类克鲁珀尔因子 15(KLF15)还能协同反式激活顺式调节模块(CRMs),从而驱动感染细胞蛋白 0(ICP0)、ICP4 和 ICP27 的表达。KLF 和特异性蛋白(Sp)家族成员结合富含 GC 或 C 的序列,属于同一超家族转录因子。基于这些观察结果,我们推测跨越 ICP0 启动子的 CRMs 会被 GR 和 Sp1 或 Sp3 转激活。在小鼠神经母细胞瘤细胞(Neuro-2A)中,CRM-A(-800至-635)、CRM-B(-485至-635)和CRM-D(-232至-24)被GR、DEX和Sp1或Sp3显著转活,而CRM-C则没有。Sp1/Sp3结合位点的突变对CRM-A和CRM-B的转激活很重要。染色质免疫沉淀研究显示,当Sp1或Sp3过度表达时,GR占据ICP0启动子序列的水平明显升高,这表明这些转录因子将GR招募到ICP0 CRM序列上。Mithramycin A 是一种抗生素,能优先结合富含 GC 的 DNA 并损害 Sp1/Sp3 依赖性转录活化,它还能减少潜伏感染 HSV-1 的小鼠从潜伏期重新激活病毒脱落。这些研究表明,GR 和某些应激诱导的细胞转录因子会优先结合富含 GC 的 DNA,从而刺激 HSV-1 基因的表达和潜伏感染小鼠三叉神经节中潜伏期病毒的重新激活。
{"title":"Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 transactivate HSV-1 ICP0 promoter sequences but a GC-rich binding antibiotic, Mithramycin A, impairs reactivation from latency","authors":"","doi":"10.1016/j.virusres.2024.199487","DOIUrl":"10.1016/j.virusres.2024.199487","url":null,"abstract":"<div><div>Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency. Furthermore, GR and Krüppel-like factor 15 (KLF15) cooperatively transactivate cis-regulatory modules (CRMs) that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. KLF and specificity protein (Sp) family members bind GC-rich or C-rich sequences and belong to the same super-family of transcription factors. Based on these observations, we hypothesized CRMs spanning the ICP0 promoter are transactivated by GR and Sp1 or Sp3. CRM-A (-800 to -635), CRM-B (-485 to -635), and CRM-D (-232 to -24), but not CRM-C, were significantly transactivated by GR, DEX, and Sp1 or Sp3 in mouse neuroblastoma cells (Neuro-2A). Mutagenesis of Sp1/Sp3 binding sites were important for transactivation of CRM-A and CRM-B. Chromatin immunoprecipitation studies revealed significantly higher levels of GR occupied ICP0 promoter sequences when Sp1 or Sp3 was over-expressed suggesting these transcriptions factors recruit GR to ICP0 CRM sequences. Mithramycin A, an antibiotic that preferentially binds GC-rich DNA and impairs Sp1/Sp3 dependent transactivation and reduced virus shedding during reactivation from latency in mice latently infected with HSV-1. These studies indicate GR and certain stress-induced cellular transcription factors preferentially bind GC rich DNA, which stimulates HSV-1 gene expression and reactivation from latency in trigeminal ganglia of latently infected mice.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Two Lytic Bacteriophages Infecting Carbapenem-Resistant Clinical Klebsiella pneumoniae in Dhaka, Bangladesh. 孟加拉国达卡感染耐碳青霉烯类临床肺炎克雷伯氏菌的两种致死性噬菌体的特征。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.virusres.2024.199491
Nishat Tasnim Ananna, Tushar Ahmed Shishir, Akash Ahmed, Syed Muktadir Al Sium, Md Salman Shakil, Dr Fahim Kabir Monjurul Haque, Md Hasanuzzaman

Bacteriophages or bacteria infecting viruses are genetically diverse. Due to the emergence of antimicrobial-resistant bacteria, lytic bacteriophages are gaining enormous attention for treating superbug infections. Klebsiella pneumoniae is one of the eight most significant nosocomial pathogens and is addressed as a critical priority pathogen by WHO, requiring alternative treatment options. We reported two highly lytic bacteriophages, Klebsiella phage Kpn BM7 and the novel Klebsiella phage Kpn BU9, isolated from hospital wastewater and exhibiting lytic activity against different clinical isolates. Whole-genome analysis revealed that phages BM7 and BU9 belong to class Caudoviricetes. Phage BM7, with a genome length of 170,558 bp, is a member of the genus Marfavirus and the species Marfavirus F48, while phage BU9, with a genome length of 60,450 bp, remains unclassified. Neither phage harbors any lysogenic, toxin, or antimicrobial resistance genes. Both phages can steadily survive up to 40°C and at pH 5-7. The optimal MOI was 0.1 for BM7 and 1 for BU9, with short latent periods of 10 and 25 min and burst sizes of 85 PFU/cell and 12 PFU/cell, respectively. This is the first carbapenem-resistant K. pneumoniae (CRKP) targeting lytic phages to be reported from Bangladesh. This study suggests that BM7 and BU9 are potential candidates for targeting carbapenem-resistant K. pneumoniae.

噬菌体或感染病毒的细菌具有基因多样性。由于抗菌细菌的出现,噬菌体在治疗超级细菌感染方面受到极大关注。肺炎克雷伯菌是八种最重要的院内病原体之一,被世界卫生组织列为关键优先病原体,需要替代治疗方案。我们报道了从医院废水中分离出的两种高溶菌性噬菌体--克雷伯氏菌噬菌体 Kpn BM7 和新型克雷伯氏菌噬菌体 Kpn BU9,它们对不同的临床分离菌株具有溶菌活性。全基因组分析表明,噬菌体 BM7 和 BU9 属于 Caudoviricetes 类。噬菌体BM7的基因组长度为170,558 bp,属于马弗病毒属和马弗病毒F48种,而噬菌体BU9的基因组长度为60,450 bp,仍未分类。两种噬菌体都不携带任何溶解基因、毒素基因或抗菌基因。两种噬菌体都能在高达 40°C 和 pH 值为 5-7 的环境中稳定存活。BM7 和 BU9 的最佳 MOI 分别为 0.1 和 1,潜伏期分别为 10 分钟和 25 分钟,迸发量分别为 85 PFU/细胞和 12 PFU/细胞。这是孟加拉国首次报道耐碳青霉烯类的肺炎双球菌(CRKP)靶向溶菌噬菌体。这项研究表明,BM7 和 BU9 是针对耐碳青霉烯类肺炎克菌的潜在候选噬菌体。
{"title":"Characterization of Two Lytic Bacteriophages Infecting Carbapenem-Resistant Clinical Klebsiella pneumoniae in Dhaka, Bangladesh.","authors":"Nishat Tasnim Ananna, Tushar Ahmed Shishir, Akash Ahmed, Syed Muktadir Al Sium, Md Salman Shakil, Dr Fahim Kabir Monjurul Haque, Md Hasanuzzaman","doi":"10.1016/j.virusres.2024.199491","DOIUrl":"https://doi.org/10.1016/j.virusres.2024.199491","url":null,"abstract":"<p><p>Bacteriophages or bacteria infecting viruses are genetically diverse. Due to the emergence of antimicrobial-resistant bacteria, lytic bacteriophages are gaining enormous attention for treating superbug infections. Klebsiella pneumoniae is one of the eight most significant nosocomial pathogens and is addressed as a critical priority pathogen by WHO, requiring alternative treatment options. We reported two highly lytic bacteriophages, Klebsiella phage Kpn BM7 and the novel Klebsiella phage Kpn BU9, isolated from hospital wastewater and exhibiting lytic activity against different clinical isolates. Whole-genome analysis revealed that phages BM7 and BU9 belong to class Caudoviricetes. Phage BM7, with a genome length of 170,558 bp, is a member of the genus Marfavirus and the species Marfavirus F48, while phage BU9, with a genome length of 60,450 bp, remains unclassified. Neither phage harbors any lysogenic, toxin, or antimicrobial resistance genes. Both phages can steadily survive up to 40°C and at pH 5-7. The optimal MOI was 0.1 for BM7 and 1 for BU9, with short latent periods of 10 and 25 min and burst sizes of 85 PFU/cell and 12 PFU/cell, respectively. This is the first carbapenem-resistant K. pneumoniae (CRKP) targeting lytic phages to be reported from Bangladesh. This study suggests that BM7 and BU9 are potential candidates for targeting carbapenem-resistant K. pneumoniae.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exceptional Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV) circulation in France in 2023 2023 年法国蓝舌病病毒 (BTV) 和流行性出血病病毒 (EHDV) 的异常流行情况。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.virusres.2024.199489
Bluetongue (BT) and Epizootic Hemorrhagic Disease (EHD) are two notifiable animal diseases transmitted to ruminants by small hematophagous midges belonging to the Culicoides genus. The etiological agents, Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV), are both members of the Sedoreoviridae family and Orbivirus genus, which include double-stranded (ds) RNA segmented genomes (10 segments). By the end of the summer 2023, first's outbreaks of EHD were reported from the south west of France, concurrently with unexpectedly severe BT cases in Central France and Corsica. Within a few weeks, numerous BT and EHD outbreaks were recorded with significant sanitary and economic impact on cattle and sheep farms (no sanitary impact of EHD for sheep). Using a customized SISPA approach and the nanopore sequencing technology we successfully recovered genomic sequences from viral isolates and blood samples from infected animals from EHD and BT outbreaks. Three different viruses were responsible for these outbreaks: EHDV-8, BTV-8 and BTV-4. The EHDV-8 strain detected in France corresponded to the strain circulating in Tunisia, Sardinia and Spain since 2021 and 2022. A new BTV-8 strain of unknown origin, clearly different from the enzootic strain circulating in France since 2015, was responsible of the BT outbreaks in domestic ruminants in 2023 on both mainland France and Corsica. A second BTV, BTV-4, also involved in BT outbreaks in Corsica, corresponded to a BTV-4 strain occasionally detected on Corsica island since 2016, suggesting either a new introduction of this strain or a silent circulation on the field. The exceptional nature of orbivirus epizootics in France in 2023, including new introduction, emergence or incursions, raises numerous questions regarding BTV and EHDV dynamics and epidemiology and stresses out the need to identify factors involved in these emergences.
蓝舌病(BT)和附红细胞体出血病(EHD)是两种应予通报的动物疾病,由属于蚋属的小型食血蠓传播给反刍动物。病原体蓝舌病病毒(BTV)和EHD病毒(Epizootic hemorrhagic disease virus)都是Sedoreoviridae科和Orbivirus属的成员,包括双链(ds)RNA片段基因组(10个片段)。到 2023 年夏末,法国西南部首次报告爆发了 EHD,与此同时,法国中部和科西嘉岛也出现了意想不到的严重 BT 病例。几周内,法国爆发了多起 BT 和 EHD疫情,对牛羊养殖场造成了严重的卫生和经济影响(EHD 对绵羊没有卫生影响)。利用定制的 SISPA 方法和纳米孔测序技术,我们成功地从 EHD 和 BT 疫情中受感染动物的病毒分离物和血液样本中恢复了基因组序列。这些疫情由三种不同的病毒引起:EHDV-8、BTV-8 和 BTV-4。在法国检测到的EHDV-8病毒株与2021年和2022年以来在突尼斯、撒丁岛和西班牙流行的病毒株一致。2023年,法国本土和科西嘉岛的家养反刍动物爆发了BT疫情,一种来源不明的新BTV-8株与2015年以来在法国流行的流行株明显不同。第二种 BTV(BTV-4)也参与了科西嘉岛的乙型肝炎疫情,它与 2016 年以来在科西嘉岛偶尔检测到的 BTV-4 株系相对应,这表明该株系要么是新引入的,要么是在野外默默流行的。2023年法国发生的口蹄疫病毒疫情(包括新传入、出现或入侵)的特殊性提出了许多有关BTV和EHDV动态和流行病学的问题,并强调有必要确定这些疫情的相关因素。
{"title":"Exceptional Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV) circulation in France in 2023","authors":"","doi":"10.1016/j.virusres.2024.199489","DOIUrl":"10.1016/j.virusres.2024.199489","url":null,"abstract":"<div><div>Bluetongue (BT) and Epizootic Hemorrhagic Disease (EHD) are two notifiable animal diseases transmitted to ruminants by small hematophagous midges belonging to the <em>Culicoides</em> genus. The etiological agents, Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV), are both members of the <em>Sedoreoviridae</em> family and <em>Orbivirus</em> genus, which include double-stranded (ds) RNA segmented genomes (10 segments). By the end of the summer 2023, first's outbreaks of EHD were reported from the south west of France, concurrently with unexpectedly severe BT cases in Central France and Corsica. Within a few weeks, numerous BT and EHD outbreaks were recorded with significant sanitary and economic impact on cattle and sheep farms (no sanitary impact of EHD for sheep). Using a customized SISPA approach and the nanopore sequencing technology we successfully recovered genomic sequences from viral isolates and blood samples from infected animals from EHD and BT outbreaks. Three different viruses were responsible for these outbreaks: EHDV-8, BTV-8 and BTV-4. The EHDV-8 strain detected in France corresponded to the strain circulating in Tunisia, Sardinia and Spain since 2021 and 2022. A new BTV-8 strain of unknown origin, clearly different from the enzootic strain circulating in France since 2015, was responsible of the BT outbreaks in domestic ruminants in 2023 on both mainland France and Corsica. A second BTV, BTV-4, also involved in BT outbreaks in Corsica, corresponded to a BTV-4 strain occasionally detected on Corsica island since 2016, suggesting either a new introduction of this strain or a silent circulation on the field. The exceptional nature of orbivirus epizootics in France in 2023, including new introduction, emergence or incursions, raises numerous questions regarding BTV and EHDV dynamics and epidemiology and stresses out the need to identify factors involved in these emergences.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic characterization and survey of a second luteovirus infecting blueberries 感染蓝莓的第二种黄体病毒的基因组特征和调查。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-10-26 DOI: 10.1016/j.virusres.2024.199480
New and emerging viral problems may be contributing to blueberry decline. In this research we described a new virus detected in Oregon blueberry production field and surveyed the region for its potential spread. The complete genome sequence of a putative new member of the genus Luteovirus was obtained from blueberry (Vaccinium corymbosum L.) by high throughput sequencing and 5′/3′-RACE. The new virus was tentatively named blueberry virus M (BlVM). Its genome is 5,018 nt long with four putative open reading frames. Similarly to some recently discovered luteoviruses, BlVM does not possess any movement protein (MP). Phylogenetic analysis confirmed clustering of BlVM with the group of non-MP luteoviruses, showing blueberry virus L as the most similar species. Through a small-scale high throughput sequencing survey we obtained 14 additional near complete genomic sequences. A larger survey of 2,654 samples by RT-PCR in Oregon and Washington (USA) found 52 BlVM-positive plants collected from four locations in Oregon. These findings will facilitate monitoring virus distribution and assessment of potential disease associated with this new and emerging blueberry virus.
新出现的病毒问题可能会导致蓝莓产量下降。在这项研究中,我们描述了在俄勒冈州蓝莓产地发现的一种新病毒,并调查了该地区的潜在传播情况。通过高通量测序和 5'/3'-RACE 技术,我们从蓝莓(Vaccinium corymbosum L.)中获得了一种假定的 Luteovirus 属新成员的完整基因组序列。新病毒被暂时命名为蓝莓病毒 M(BlVM)。它的基因组长 5,018 nt,有四个推测的开放阅读框。与最近发现的一些黄体病毒类似,BlVM不具有任何运动蛋白(MP)。系统进化分析证实,BlVM 与无运动蛋白的黄体病毒群聚类,显示蓝莓病毒 L(BlVL)是最相似的物种。通过小规模的高通量测序调查,我们又获得了 14 个接近完整的基因组序列。通过 RT-PCR 技术对美国俄勒冈州和华盛顿州的 2,654 份样本进行了更大规模的调查,发现从俄勒冈州的四个地点采集的 52 株 BlVM 阳性植株。这些发现将有助于监测病毒的分布情况,并评估与这种新出现的蓝莓病毒相关的潜在疾病。
{"title":"Genomic characterization and survey of a second luteovirus infecting blueberries","authors":"","doi":"10.1016/j.virusres.2024.199480","DOIUrl":"10.1016/j.virusres.2024.199480","url":null,"abstract":"<div><div>New and emerging viral problems may be contributing to blueberry decline. In this research we described a new virus detected in Oregon blueberry production field and surveyed the region for its potential spread. The complete genome sequence of a putative new member of the genus <em>Luteovirus</em> was obtained from blueberry (<em>Vaccinium corymbosum</em> L.) by high throughput sequencing and 5′/3′-RACE. The new virus was tentatively named blueberry virus M (BlVM). Its genome is 5,018 nt long with four putative open reading frames. Similarly to some recently discovered luteoviruses, BlVM does not possess any movement protein (MP). Phylogenetic analysis confirmed clustering of BlVM with the group of non-MP luteoviruses, showing blueberry virus L as the most similar species. Through a small-scale high throughput sequencing survey we obtained 14 additional near complete genomic sequences. A larger survey of 2,654 samples by RT-PCR in Oregon and Washington (USA) found 52 BlVM-positive plants collected from four locations in Oregon. These findings will facilitate monitoring virus distribution and assessment of potential disease associated with this new and emerging blueberry virus.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats 病毒化石的特征:了解蝙蝠内源性逆转录病毒多样性的比较基因组学方法。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.virusres.2024.199484
Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.
内源性逆转录病毒(ERV)是脊椎动物基因组中常见的过去病毒感染的痕迹。许多 ERV 受到宿主基因组的严格调控,并在宿主体内发挥各种功能。蝙蝠是唯一真正的易变哺乳动物,拥有哺乳动物中最小的基因组,基因组中ERV的比例很高。它们是各种人畜共患病毒病原体的重要宿主,能有效调节自身的免疫反应,耐受病毒感染。逆转录病毒的整合被认为是蝙蝠共同进化对抗病毒感染策略的机制之一。在这项研究中,我们调查了40多个公开蝙蝠基因组中ERV的多样性,以了解ERV在蝙蝠体内的分布和进化。我们在蝙蝠基因组中观察到了所有类别的ERV,甚至包括复杂的lenti逆转录病毒。通常被认为在哺乳动物中罕见的α和spuma逆转录病毒在蝙蝠中很常见。我们观察到,蝙蝠基因组的大小与ERV元件的长度呈正相关。有趣的是,蝙蝠体内近30%的ERV都是完整的,这表明ERV是最近才起源的,或者是被宿主基因组共用的。未来的研究将侧重于比较基因组和实验数据,这对了解这些ERV在宿主基因组进化中的作用至关重要。
{"title":"Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats","authors":"","doi":"10.1016/j.virusres.2024.199484","DOIUrl":"10.1016/j.virusres.2024.199484","url":null,"abstract":"<div><div>Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies 人类诺如病毒研究进展:疫苗、基因型分布和抗病毒策略。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-10-23 DOI: 10.1016/j.virusres.2024.199486
Norovirus, belonging to the Caliciviridae family, is a non-enveloped, positive-sense single-stranded RNA virus. It is widely acknowledged as a significant etiological agent responsible for non-bacterial acute gastroenteritis and considered a major cause thereof. Norovirus is primarily tranmitted via fecal-oral route, but can also be transmitted via airborne routes. Clinical manifestations often include symptoms associated with acute gastroenteritis, like nausea, vomiting, watery diarrhea, stomach cramps, and others. Due to the specific pathogenic mechanism of the virus, and genomic diversity, there are currently no preventive vaccines or effective antiviral drugs available for treating norovirus-induced acute gastroenteritis infections. The management of such infections mainly relies on oral rehydration therapy while prevention necessitates adherence to personal hygiene measures.
The present paper discusses the nature, transmission route, clinical manifestations, immune response mechanism, and vaccine research of Norovirus. The objective of this review manuscript is to systematically gather, analyze, and summarize recent research and investigations on norovirus in order to enhance our understanding of its characteristics and pathogenesis. This not only facilitates subsequent researchers in acquiring a more expedited and comprehensive grasp of the existing knowledge about norovirus but also provides clearer directions and goals for future studies.
诺如病毒属于卡里科病毒属,是一种无包膜的正义单链 RNA 病毒。人们普遍认为它是导致非细菌性急性肠胃炎的重要病原体,并认为它是导致非细菌性急性肠胃炎的主要原因。诺如病毒主要通过粪-口途径传播,但也可通过空气传播。临床表现通常包括与急性肠胃炎相关的症状,如恶心、呕吐、水样腹泻、胃痉挛等。由于诺如病毒具有特殊的致病机制和基因组多样性,目前还没有预防性疫苗或有效的抗病毒药物可用于治疗诺如病毒引起的急性肠胃炎感染。治疗这类感染主要依靠口服补液疗法,而预防则需要坚持个人卫生措施。本文讨论了诺如病毒的性质、传播途径、临床表现、免疫反应机制和疫苗研究。本综述手稿旨在系统地收集、分析和总结近期有关诺如病毒的研究和调查,以加深我们对其特征和发病机制的了解。这不仅有助于后续研究人员更快、更全面地掌握诺如病毒的现有知识,也为今后的研究提供了更明确的方向和目标。
{"title":"Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies","authors":"","doi":"10.1016/j.virusres.2024.199486","DOIUrl":"10.1016/j.virusres.2024.199486","url":null,"abstract":"<div><div><em>Norovirus</em>, belonging to the <em>Caliciviridae</em> family, is a non-enveloped, positive-sense single-stranded RNA virus. It is widely acknowledged as a significant etiological agent responsible for non-bacterial acute gastroenteritis and considered a major cause thereof. <em>Norovirus</em> is primarily tranmitted via fecal-oral route, but can also be transmitted via airborne routes. Clinical manifestations often include symptoms associated with acute gastroenteritis, like nausea, vomiting, watery diarrhea, stomach cramps, and others. Due to the specific pathogenic mechanism of the virus, and genomic diversity, there are currently no preventive vaccines or effective antiviral drugs available for treating norovirus-induced acute gastroenteritis infections. The management of such infections mainly relies on oral rehydration therapy while prevention necessitates adherence to personal hygiene measures.</div><div>The present paper discusses the nature, transmission route, clinical manifestations, immune response mechanism, and vaccine research of <em>Norovirus</em>. The objective of this review manuscript is to systematically gather, analyze, and summarize recent research and investigations on norovirus in order to enhance our understanding of its characteristics and pathogenesis. This not only facilitates subsequent researchers in acquiring a more expedited and comprehensive grasp of the existing knowledge about norovirus but also provides clearer directions and goals for future studies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of novel phage pK3–24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae 针对耐多药肺炎克雷伯氏菌的新型噬菌体pK3-24的特征及其对鼠胆幼虫的疗效。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.virusres.2024.199481
Klebsiella pneumoniae is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3–24, that mainly targets ST447 K. pneumoniae. Phage pK3–24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3–24 shows environmental stability, surviving at below 50 °C and at pH values of 6–10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3–24 to the genus Przondovirus as a new species. Phage pK3–24 inhibited the production of biofilm. Moreover, treatment with pK3–24 at doses with an MOI > 1 effectively reduced the mortality of Galleria mellonella larvae infected with ST447 K. pneumoniae.
肺炎克雷伯氏菌是一种常见的条件致病菌,通常具有耐多药表型,导致抗生素治疗失败。因此,它可能诱发严重疾病,包括社区获得性肺炎和血流感染。作为抗生素的新兴替代品,噬菌体被认为是解决耐药细菌感染问题的关键。在这里,我们报告了一种主要针对 ST447 肺炎克氏菌的新型噬菌体 pK3-24。pK3-24 是一种类似 T7 的短尾噬菌体,具有快速吸附能力,能在细菌草坪上形成带晕的半透明斑块。最佳感染倍数(MOI)为 0.01,平均迸发量为 50 PFU/mL。pK3-24 噬菌体具有环境稳定性,可在低于 50 °C 和 pH 值为 6-10 的环境中存活。它的双链 DNA 基因组为 40,327 bp,不携带抗生素抗性、毒力或溶菌基因。系统进化分析将 pK3-24 噬菌体归入 Przondovirus 属,成为一个新物种。pK3-24 噬菌体能抑制生物膜的产生。此外,以 MOI > 1 的剂量使用 pK3-24 能有效降低感染 ST447 肺炎双球菌的 Galleria mellonella 幼虫的死亡率。
{"title":"Characterization of novel phage pK3–24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae","authors":"","doi":"10.1016/j.virusres.2024.199481","DOIUrl":"10.1016/j.virusres.2024.199481","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3–24, that mainly targets ST447 <em>K. pneumoniae</em>. Phage pK3–24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3–24 shows environmental stability, surviving at below 50 °C and at pH values of 6–10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3–24 to the genus <em>Przondovirus</em> as a new species. Phage pK3–24 inhibited the production of biofilm. Moreover, treatment with pK3–24 at doses with an MOI &gt; 1 effectively reduced the mortality of <em>Galleria mellonella</em> larvae infected with ST447 <em>K. pneumoniae</em>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin 二氢霉素通过抑制螯合蛋白酶 L 和呋喃蛋白酶,对 SARS-CoV-2 的进入起到双管齐下的作用。
IF 2.5 4区 医学 Q3 VIROLOGY Pub Date : 2024-10-19 DOI: 10.1016/j.virusres.2024.199485
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.
严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引发了冠状病毒病 2019(COVID-19)大流行,对全球健康构成严重威胁。目前,治疗 COVID-19 的有效广谱抗病毒药物尚不充足。在本研究中,我们研究了天然木质素二氢叶黄素(PubChem CID 100492)对不同SARS-CoV-2变体的抗病毒活性,并探索了其潜在的分子机制。我们发现,Diphyllin 能剂量依赖性地抑制 SARS-CoV-2 穗状病毒(S)介导的病毒进入不同类型的细胞。这种强效抑制作用对源自原始 SARS-CoV-2 和相关变体(如 Alpha、Beta、Delta 或 Omicron)的尖峰蛋白非常明显。因此,二氢叶绿素还能显著抑制临床 SARS-CoV-2 病毒分离株的体外感染。从机理上讲,通过中和内质体酸化和降低半胱氨酸蛋白酶 cathepsin L (CTSL) 的活性,diphyllin 同时抑制了 SARS-CoV-2 的内质体进入,并通过损害呋喃蛋白酶的活性抑制了 S 介导的细胞表面进入。总之,我们的研究结果表明,diphyllin 是一种新型的 CTSL 和 furin 蛋白酶抑制剂,能双管齐下地阻止 SARS-CoV-2 沿内体和细胞表面途径进入细胞。因此,Diphyllin 有可能作为一种抑制 SARS-CoV-2 进入的药物而得到推广。
{"title":"Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin","authors":"","doi":"10.1016/j.virusres.2024.199485","DOIUrl":"10.1016/j.virusres.2024.199485","url":null,"abstract":"<div><div>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (<em>S</em>)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron<em>.</em> Accordingly, diphyllin also significantly inhibited the <em>in vitro</em> infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Virus research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1