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Persistent viral RNA and protein contribute to post-acute pathology 持续存在的病毒 RNA 和蛋白质导致了急性期后的病理变化
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01837-0
Keng Yih Chew, Kirsty R. Short
{"title":"Persistent viral RNA and protein contribute to post-acute pathology","authors":"Keng Yih Chew, Kirsty R. Short","doi":"10.1038/s41564-024-01837-0","DOIUrl":"10.1038/s41564-024-01837-0","url":null,"abstract":"Viral RNA and protein are found to persist in infected lungs and contribute to post-acute pathology in Sendai virus infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2797-2798"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Guiding phage therapy with genomic surveillance 用基因组监测指导噬菌体疗法
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01836-1
Lorenz Leitner, Shawna McCallin
{"title":"Guiding phage therapy with genomic surveillance","authors":"Lorenz Leitner, Shawna McCallin","doi":"10.1038/s41564-024-01836-1","DOIUrl":"10.1038/s41564-024-01836-1","url":null,"abstract":"Integrating global and local genomic surveillance into phage therapy cocktail design offers a middle ground between personalized and product-based treatment options.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2799-2800"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PcdA promotes orthogonal division plane selection in Staphylococcus aureus PcdA 促进金黄色葡萄球菌的正交分裂面选择
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-28 DOI: 10.1038/s41564-024-01821-8
Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi
{"title":"PcdA promotes orthogonal division plane selection in Staphylococcus aureus","authors":"Félix Ramos-León, Brandon R. Anjuwon-Foster, Vivek Anantharaman, Taylor B. Updegrove, Colby N. Ferreira, Amany M. Ibrahim, Chin-Hsien Tai, Michael J. Kruhlak, Dominique M. Missiakas, Jodi L. Camberg, L. Aravind, Kumaran S. Ramamurthi","doi":"10.1038/s41564-024-01821-8","DOIUrl":"10.1038/s41564-024-01821-8","url":null,"abstract":"The bacterial pathogen, Staphylococcus aureus, grows by dividing in two alternating orthogonal planes. How these cell division planes are positioned correctly is not known. Here we used chemical genetic screening to identify PcdA as a division plane placement factor. Molecular biology and imaging approaches revealed non-orthogonal division plane selection for pcdA mutant bacteria. PcdA is a structurally and functionally altered member of the McrB AAA+ NTPase family, which are often found as restriction enzyme subunits. PcdA interacts with the tubulin-like divisome component, FtsZ, and the structural protein, DivIVA; it also localizes to future cell division sites. PcdA multimerization, localization and function are NTPase activity-dependent. We propose that the DivIVA/PcdA complex recruits unpolymerized FtsZ to assemble along the proper cell division plane. Although pcdA deletion did not affect S. aureus growth in several laboratory conditions, its clustered growth pattern was disrupted, sensitivity to cell-wall-targeting antibiotics increased and virulence in mice decreased. We propose that the characteristic clustered growth pattern of S. aureus, which emerges from dividing in alternating orthogonal division planes, might protect the bacterium from host defences. PcdA interacts with DivIVA and FtsZ, promoting Z-ring formation and division plane selection in Staphylococcus aureus, which increases virulence in mice and reduces sensitivity to cell-wall-targeting antibiotics.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2997-3012"},"PeriodicalIF":20.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection 在气道感染过程中,铜绿假单胞菌面临着粘膜定植和抗生素耐受性之间的适应性权衡
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-25 DOI: 10.1038/s41564-024-01842-3
Lucas A. Meirelles, Evangelia Vayena, Auriane Debache, Eric Schmidt, Tamara Rossy, Tania Distler, Vassily Hatzimanikatis, Alexandre Persat
{"title":"Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection","authors":"Lucas A. Meirelles, Evangelia Vayena, Auriane Debache, Eric Schmidt, Tamara Rossy, Tania Distler, Vassily Hatzimanikatis, Alexandre Persat","doi":"10.1038/s41564-024-01842-3","DOIUrl":"10.1038/s41564-024-01842-3","url":null,"abstract":"Pseudomonas aeruginosa frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated P. aeruginosa growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq). Metabolic modelling based on Tn-seq data revealed the nutritional requirements for P. aeruginosa growth, highlighting reliance on glucose and lactate and varying requirements for amino acid biosynthesis. Tn-seq also revealed selection against biofilm formation during mucosal growth in the absence of antibiotics. Live imaging in engineered organoids showed that biofilm-dwelling cells remained sessile while colonizing the mucosal surface, limiting nutrient foraging and reduced growth. Conversely, biofilm formation increased antibiotic tolerance at the mucosal surface. Moreover, mutants with exacerbated biofilm phenotypes protected less tolerant but more cytotoxic strains, contributing to phenotypic heterogeneity. P. aeruginosa must therefore navigate conflicting physical and biological selective pressures to establish chronic infections. Tn-seq and live imaging of Pseudomonas aeruginosa during airway epithelial organoid infections reveal metabolic adaptations and trade-offs between growth and antibiotic tolerance in biofilm lifestyle, impacting bacterial spread and cytotoxicity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3284-3303"},"PeriodicalIF":20.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metagenomic characterization of viruses and mobile genetic elements associated with the DPANN archaeal superphylum 与 DPANN 古菌超门相关的病毒和移动遗传元素的元基因组特征
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-24 DOI: 10.1038/s41564-024-01839-y
Zongzhi Wu, Shufeng Liu, Jinren Ni
{"title":"Metagenomic characterization of viruses and mobile genetic elements associated with the DPANN archaeal superphylum","authors":"Zongzhi Wu, Shufeng Liu, Jinren Ni","doi":"10.1038/s41564-024-01839-y","DOIUrl":"10.1038/s41564-024-01839-y","url":null,"abstract":"The archaeal superphylum DPANN (an acronym formed from the initials of the first five phyla discovered: Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanohaloarchaeota and Nanoarchaeota) is a group of ultrasmall symbionts able to survive in extreme ecosystems. The diversity and dynamics between DPANN archaea and their virome remain largely unknown. Here we use a metagenomic clustered regularly interspaced short palindromic repeats (CRISPR) screening approach to identify 97 globally distributed, non-redundant viruses and unclassified mobile genetic elements predicted to infect hosts across 8 DPANN phyla, including 7 viral groups not previously characterized. Genomic analysis suggests a diversity of viral morphologies including head-tailed, tailless icosahedral and spindle-shaped viruses with the potential to establish lytic, chronic or lysogenic infections. We also find evidence of a virally encoded Cas12f1 protein (probably originating from uncultured DPANN archaea) and a mini-CRISPR array, which could play a role in modulating host metabolism. Many metagenomes have virus-to-host ratios >10, indicating that DPANN viruses play an important role in controlling host populations. Overall, our study illuminates the underexplored diversity, functional repertoires and host interactions of the DPANN virome. A metagenomic CRISPR screening approach identifies an expansive diversity of viruses and mobile genetic elements infecting the enigmatic ultrasmall DPANN archaea.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3362-3375"},"PeriodicalIF":20.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools Gamma-Mobile-Trio 系统是富含细菌防御和进攻工具的移动元件
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-23 DOI: 10.1038/s41564-024-01840-5
Tridib Mahata, Katarzyna Kanarek, Moran G. Goren, Rameshkumar Marimuthu Ragavan, Eran Bosis, Udi Qimron, Dor Salomon
{"title":"Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools","authors":"Tridib Mahata, Katarzyna Kanarek, Moran G. Goren, Rameshkumar Marimuthu Ragavan, Eran Bosis, Udi Qimron, Dor Salomon","doi":"10.1038/s41564-024-01840-5","DOIUrl":"10.1038/s41564-024-01840-5","url":null,"abstract":"The evolutionary arms race between bacteria and phages led to the emergence of bacterial immune systems whose diversity and dynamics remain poorly understood. Here we use comparative genomics to describe a widespread genetic element, defined by the presence of the Gamma-Mobile-Trio (GMT) proteins, that serves as a reservoir of offensive and defensive tools. We demonstrate, using Vibrio parahaemolyticus as a model, that GMT-containing genomic islands are active mobile elements. Furthermore, we show that GMT islands’ cargoes contain various anti-phage defence systems, antibacterial type VI secretion system (T6SS) effectors and antibiotic-resistance genes. We reveal four anti-phage defence systems encoded within GMT islands and further characterize one system, GAPS1, showing it is triggered by a phage capsid protein to induce cell dormancy. Our findings underscore the need to broaden the concept of ‘defence islands’ to include defensive and offensive tools, as both share the same mobile elements for dissemination. GMT-containing genomic islands in Vibrio parahaemolyticus and other diverse bacteria serve as a stockpile of immune and anti-phage defence systems, antibiotic-resistance genes and offensive tools such as type VI secretion system effectors.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 12","pages":"3268-3283"},"PeriodicalIF":20.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic discovery of antibacterial and antifungal bacterial toxins 抗菌和抗真菌细菌毒素的系统发现
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-22 DOI: 10.1038/s41564-024-01820-9
Nimrod Nachmias, Noam Dotan, Marina Campos Rocha, Rina Fraenkel, Katharina Detert, Monika Kluzek, Maor Shalom, Shani Cheskis, Sonu Peedikayil-Kurien, Gilad Meitav, Arbel Rivitz, Naama Shamash-Halevy, Inbar Cahana, Noam Deouell, Jacob Klein, Meital Oren-Suissa, Herbert Schmidt, Neta Schlezinger, Netanel Tzarum, Yaara Oppenheimer-Shaanan, Asaf Levy
{"title":"Systematic discovery of antibacterial and antifungal bacterial toxins","authors":"Nimrod Nachmias, Noam Dotan, Marina Campos Rocha, Rina Fraenkel, Katharina Detert, Monika Kluzek, Maor Shalom, Shani Cheskis, Sonu Peedikayil-Kurien, Gilad Meitav, Arbel Rivitz, Naama Shamash-Halevy, Inbar Cahana, Noam Deouell, Jacob Klein, Meital Oren-Suissa, Herbert Schmidt, Neta Schlezinger, Netanel Tzarum, Yaara Oppenheimer-Shaanan, Asaf Levy","doi":"10.1038/s41564-024-01820-9","DOIUrl":"10.1038/s41564-024-01820-9","url":null,"abstract":"Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin–immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications. Genome sequence mining and computational analyses lead to the discovery and functional characterization of conserved bacterial toxins with activity against bacteria and fungi.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3041-3058"},"PeriodicalIF":20.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep mining reveals the diversity of endogenous viral elements in vertebrate genomes 深度挖掘揭示脊椎动物基因组中内源性病毒元件的多样性
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-22 DOI: 10.1038/s41564-024-01825-4
Jose Gabriel Nino Barreat, Aris Katzourakis
{"title":"Deep mining reveals the diversity of endogenous viral elements in vertebrate genomes","authors":"Jose Gabriel Nino Barreat, Aris Katzourakis","doi":"10.1038/s41564-024-01825-4","DOIUrl":"10.1038/s41564-024-01825-4","url":null,"abstract":"Integration of viruses into host genomes can give rise to endogenous viral elements (EVEs), which provide insights into viral diversity, host range and evolution. A systematic search for EVEs is becoming computationally challenging given the available genomic data. We used a cloud-computing approach to perform a comprehensive search for EVEs in the kingdoms Shotokuvirae and Orthornavirae across vertebrates. We identified 2,040 EVEs in 295 vertebrate genomes and provide evidence for EVEs belonging to the families Chuviridae, Paramyxoviridae, Nairoviridae and Benyviridae. We also find an EVE from the Hepacivirus genus of flaviviruses with orthology across murine rodents. In addition, our analyses revealed that reptarenaviruses and filoviruses probably acquired their glycoprotein ectodomains three times independently from retroviral elements. Taken together, these findings encourage the addition of 4 virus families and the Hepacivirus genus to the growing virus fossil record of vertebrates, providing key insights into their natural history and evolution. Computational cloud-based screen of vertebrate genomes identifies endogenous viral elements of members of the kingdoms Shotokuvirae and Orthornavirae and informs about evolutionary history of non-retroviral elements.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3013-3024"},"PeriodicalIF":20.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01825-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men 对 3 137 名男性口腔人类乳头瘤病毒发病率的多国流行病学分析
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-18 DOI: 10.1038/s41564-024-01824-5
Racheal S. Dube Mandishora, Brittney L. Dickey, Wenyi Fan, Bradley Sirak, Kimberly Isaacs-Soriano, Julie Rathwell, Martha Abrahamsen, Richard R. Reich, Michael J. Schell, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna R. Giuliano
{"title":"Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men","authors":"Racheal S. Dube Mandishora, Brittney L. Dickey, Wenyi Fan, Bradley Sirak, Kimberly Isaacs-Soriano, Julie Rathwell, Martha Abrahamsen, Richard R. Reich, Michael J. Schell, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna R. Giuliano","doi":"10.1038/s41564-024-01824-5","DOIUrl":"10.1038/s41564-024-01824-5","url":null,"abstract":"Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence. Multinational analysis of oral human papillomavirus infection incidence and associated factors in 3,137 men reveals infection risk is maintained throughout lifetime, with implications for vaccination strategies.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2836-2846"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2 具有广泛治疗作用的抗体通过 Fc 效应器功能和模拟 SCARB2 提供针对肠道病毒的跨血清型保护
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-10-18 DOI: 10.1038/s41564-024-01822-7
Rui Zhu, Yuanyuan Wu, Yang Huang, Yanan Jiang, Yichao Jiang, Dongqing Zhang, Hui Sun, Zhenhong Zhou, Lizhi Zhou, Shihan Weng, Hao Chen, Xiaoqing Chen, Wenjing Ning, Yuxiang Zou, Maozhou He, Hongwei Yang, Weixi Deng, Yu Li, Zhenqin Chen, Xiangzhong Ye, Jinle Han, Zhichao Yin, Huan Zhao, Che Liu, Yuqiong Que, Mujin Fang, Hai Yu, Jun Zhang, Wenxin Luo, Shaowei Li, Qingbing Zheng, Longfa Xu, Ningshao Xia, Tong Cheng
{"title":"Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2","authors":"Rui Zhu, Yuanyuan Wu, Yang Huang, Yanan Jiang, Yichao Jiang, Dongqing Zhang, Hui Sun, Zhenhong Zhou, Lizhi Zhou, Shihan Weng, Hao Chen, Xiaoqing Chen, Wenjing Ning, Yuxiang Zou, Maozhou He, Hongwei Yang, Weixi Deng, Yu Li, Zhenqin Chen, Xiangzhong Ye, Jinle Han, Zhichao Yin, Huan Zhao, Che Liu, Yuqiong Que, Mujin Fang, Hai Yu, Jun Zhang, Wenxin Luo, Shaowei Li, Qingbing Zheng, Longfa Xu, Ningshao Xia, Tong Cheng","doi":"10.1038/s41564-024-01822-7","DOIUrl":"10.1038/s41564-024-01822-7","url":null,"abstract":"Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus–receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion–SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine. Identification of a broadly therapeutic antibody h1A6.2 against enteroviruses, which mimics the entry receptor SCARB2 and triggers monocyte/macrophage-dependent Fc effector functions in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2939-2953"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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