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Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts 寄生线虫的多种 RNA 病毒可引起脊椎动物宿主的抗体反应
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-09-04 DOI: 10.1038/s41564-024-01796-6
Shannon Quek, Amber Hadermann, Yang Wu, Lander De Coninck, Shrilakshmi Hegde, Jordan R. Boucher, Jessica Cresswell, Ella Foreman, Andrew Steven, E. James LaCourse, Stephen A. Ward, Samuel Wanji, Grant L. Hughes, Edward I. Patterson, Simon C. Wagstaff, Joseph D. Turner, Rhys H. Parry, Alain Kohl, Eva Heinz, Kenneth Bentum Otabil, Jelle Matthijnssens, Robert Colebunders, Mark J. Taylor
{"title":"Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts","authors":"Shannon Quek, Amber Hadermann, Yang Wu, Lander De Coninck, Shrilakshmi Hegde, Jordan R. Boucher, Jessica Cresswell, Ella Foreman, Andrew Steven, E. James LaCourse, Stephen A. Ward, Samuel Wanji, Grant L. Hughes, Edward I. Patterson, Simon C. Wagstaff, Joseph D. Turner, Rhys H. Parry, Alain Kohl, Eva Heinz, Kenneth Bentum Otabil, Jelle Matthijnssens, Robert Colebunders, Mark J. Taylor","doi":"10.1038/s41564-024-01796-6","DOIUrl":"10.1038/s41564-024-01796-6","url":null,"abstract":"Parasitic nematodes have an intimate, chronic and lifelong exposure to vertebrate tissues. Here we mined 41 published parasitic nematode transcriptomes from vertebrate hosts and identified 91 RNA viruses across 13 virus orders from 24 families in ~70% (28 out of 41) of parasitic nematode species, which include only 5 previously reported viruses. We observe widespread distribution of virus–nematode associations across multiple continents, suggesting an ancestral acquisition event and host–virus co-evolution. Characterization of viruses of Brugia malayi (BMRV1) and Onchocerca volvulus (OVRV1) shows that these viruses are abundant in reproductive tissues of adult parasites. Importantly, the presence of BMRV1 RNA in B. malayi parasites mounts an RNA interference response against BMRV1 suggesting active viral replication. Finally, BMRV1 and OVRV1 were found to elicit antibody responses in serum samples from infected jirds and infected or exposed humans, indicating direct exposure to the immune system. Transcriptome mining, phylogenetic analysis, bioimaging and serology experiments reveal a widespread diverse virome present in ~70% of parasitic nematodes, such as Brugia malayi and Onchocerca volvulus, where some viruses are abundant in the reproductive tract and are associated with seropositivity in vertebrate hosts.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2488-2505"},"PeriodicalIF":20.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01796-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130795","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
We must learn from past outbreaks 我们必须从过去的疫情中吸取教训。
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-09-03 DOI: 10.1038/s41564-024-01813-8
{"title":"We must learn from past outbreaks","authors":"","doi":"10.1038/s41564-024-01813-8","DOIUrl":"10.1038/s41564-024-01813-8","url":null,"abstract":"To successfully tackle the current mpox public-health emergency, we must learn from past outbreaks to focus research questions and take collaborative action.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2201-2201"},"PeriodicalIF":20.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01813-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126223","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
Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans 单细胞检测拷贝数变化揭示白念珠菌对抗真菌药物的动态适应机制
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-09-03 DOI: 10.1038/s41564-024-01795-7
Xin Zhou, Audrey Hilk, Norma V. Solis, Nancy Scott, Annette Beach, Natthapon Soisangwan, Clara L. Billings, Laura S. Burrack, Scott G. Filler, Anna Selmecki
{"title":"Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans","authors":"Xin Zhou, Audrey Hilk, Norma V. Solis, Nancy Scott, Annette Beach, Natthapon Soisangwan, Clara L. Billings, Laura S. Burrack, Scott G. Filler, Anna Selmecki","doi":"10.1038/s41564-024-01795-7","DOIUrl":"10.1038/s41564-024-01795-7","url":null,"abstract":"Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo. Development of a dual-fluorescent reporter system allows rapid quantification of diverse genomic copy number changes that arise in Candida albicans during adaptation to antifungal drugs.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2923-2938"},"PeriodicalIF":20.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123706","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
Individual bacterial cells can use spatial sensing of chemical gradients to direct chemotaxis on surfaces 单个细菌细胞可以利用对化学梯度的空间感知来引导表面的趋化运动
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-09-02 DOI: 10.1038/s41564-024-01729-3
James H. R. Wheeler, Kevin R. Foster, William M. Durham
{"title":"Individual bacterial cells can use spatial sensing of chemical gradients to direct chemotaxis on surfaces","authors":"James H. R. Wheeler, Kevin R. Foster, William M. Durham","doi":"10.1038/s41564-024-01729-3","DOIUrl":"10.1038/s41564-024-01729-3","url":null,"abstract":"Swimming bacteria navigate chemical gradients using temporal sensing to detect changes in concentration over time. Here we show that surface-attached bacteria use a fundamentally different mode of sensing during chemotaxis. We combined microfluidic experiments, massively parallel cell tracking and fluorescent reporters to study how Pseudomonas aeruginosa senses chemical gradients during pili-based ‘twitching’ chemotaxis on surfaces. Unlike swimming cells, we found that temporal changes in concentration did not induce motility changes in twitching cells. We then quantified the chemotactic behaviour of stationary cells by following changes in the sub-cellular localization of fluorescent proteins as cells are exposed to a gradient that alternates direction. These experiments revealed that P. aeruginosa cells can directly sense differences in concentration across the lengths of their bodies, even in the presence of strong temporal fluctuations. Our work thus overturns the widely held notion that bacterial cells are too small to directly sense chemical gradients in space. Microfluidic experiments reveal that surface-attached Pseudomonas aeruginosa cells directly sense differences in chemical concentration across the length of their cell bodies to guide pili-based chemotaxis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2308-2322"},"PeriodicalIF":20.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01729-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118126","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
Neurospora intermedia from a traditional fermented food enables waste-to-food conversion 从传统发酵食品中提取的中间神经孢子菌实现了变废为宝
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-29 DOI: 10.1038/s41564-024-01799-3
Vayu Maini Rekdal, José Manuel Villalobos-Escobedo, Nabila Rodriguez-Valeron, Mikel Olaizola Garcia, Diego Prado Vásquez, Alexander Rosales, Pia M. Sörensen, Edward E. K. Baidoo, Ana Calheiros de Carvalho, Robert Riley, Anna Lipzen, Guifen He, Mi Yan, Sajeet Haridas, Christopher Daum, Yuko Yoshinaga, Vivian Ng, Igor V. Grigoriev, Rasmus Munk, Christofora Hanny Wijaya, Lilis Nuraida, Isty Damayanti, Pablo Cruz-Morales, Jay. D. Keasling
{"title":"Neurospora intermedia from a traditional fermented food enables waste-to-food conversion","authors":"Vayu Maini Rekdal, José Manuel Villalobos-Escobedo, Nabila Rodriguez-Valeron, Mikel Olaizola Garcia, Diego Prado Vásquez, Alexander Rosales, Pia M. Sörensen, Edward E. K. Baidoo, Ana Calheiros de Carvalho, Robert Riley, Anna Lipzen, Guifen He, Mi Yan, Sajeet Haridas, Christopher Daum, Yuko Yoshinaga, Vivian Ng, Igor V. Grigoriev, Rasmus Munk, Christofora Hanny Wijaya, Lilis Nuraida, Isty Damayanti, Pablo Cruz-Morales, Jay. D. Keasling","doi":"10.1038/s41564-024-01799-3","DOIUrl":"10.1038/s41564-024-01799-3","url":null,"abstract":"Fungal fermentation of food and agricultural by-products holds promise for improving food sustainability and security. However, the molecular basis of fungal waste-to-food upcycling remains poorly understood. Here we use a multi-omics approach to characterize oncom, a fermented food traditionally produced from soymilk by-products in Java, Indonesia. Metagenomic sequencing of samples from small-scale producers in Western Java indicated that the fungus Neurospora intermedia dominates oncom. Further transcriptomic, metabolomic and phylogenomic analysis revealed that oncom-derived N. intermedia utilizes pectin and cellulose degradation during fermentation and belongs to a genetically distinct subpopulation associated with human-generated by-products. Finally, we found that N. intermedia grew on diverse by-products such as fruit and vegetable pomace and plant-based milk waste, did not encode mycotoxins, and could create foods that were positively perceived by consumers outside Indonesia. These results showcase the traditional significance and future potential of fungal fermentation for creating delicious and nutritious foods from readily available by-products. A multi-omics analysis of oncom, an Indonesian fermented food made from soymilk waste, shows how associated fungi break down food waste to yield nutritious and positively received foods.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2666-2683"},"PeriodicalIF":20.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01799-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089949","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
An S-methyltransferase that produces the climate-active gas dimethylsulfide is widespread across diverse marine bacteria 产生气候活性气体二甲基硫醚的 S-甲基转移酶广泛存在于各种海洋细菌中
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-28 DOI: 10.1038/s41564-024-01788-6
Yunhui Zhang, Chuang Sun, Zihua Guo, Liyan Liu, Xiaotong Zhang, Kai Sun, Yanfen Zheng, Andrew J. Gates, Jonathan D. Todd, Xiao-Hua Zhang
{"title":"An S-methyltransferase that produces the climate-active gas dimethylsulfide is widespread across diverse marine bacteria","authors":"Yunhui Zhang, Chuang Sun, Zihua Guo, Liyan Liu, Xiaotong Zhang, Kai Sun, Yanfen Zheng, Andrew J. Gates, Jonathan D. Todd, Xiao-Hua Zhang","doi":"10.1038/s41564-024-01788-6","DOIUrl":"10.1038/s41564-024-01788-6","url":null,"abstract":"Hydrogen sulfide (H2S), methanethiol (MeSH) and dimethylsulfide (DMS) are abundant sulfur gases with roles in biogeochemical cycling, chemotaxis and/or climate regulation. Catabolism of the marine osmolyte dimethylsulfoniopropionate (DMSP) is a major source of DMS and MeSH, but both also result from S-methylation of H2S via MddA, an H2S and MeSH S-methyltransferase whose gene is abundant in soil but scarce in marine environments. Here we identify the S-adenosine methionine (SAM)-dependent MeSH and H2S S-methyltransferase ‘MddH’, which is widespread in diverse marine bacteria and some freshwater and soil bacteria. mddH is predicted in up to ~5% and ~15% of seawater and coastal sediment bacteria, respectively, which is considerably higher than mddA. Furthermore, marine mddH transcript levels are similar to those for the most abundant DMSP lyase gene dddP. This study implies that the importance of H2S and MeSH S-methylation pathways in marine environments is significantly underestimated. The S-methyltransferase enzyme MddH produces DMS from hydrogen sulfide and methanethiol and its gene abundance rivals that of other known genes whose products generate DMS in marine environments.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2614-2625"},"PeriodicalIF":20.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01788-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085509","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
Understanding emerging and re-emerging viruses to facilitate pandemic preparedness 了解新出现和再次出现的病毒,促进大流行病防备工作
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-28 DOI: 10.1038/s41564-024-01789-5
Francisco J. Zapatero-Belinchón, Priti Kumar, Melanie Ott, Olivier Schwartz, Alex Sigal
{"title":"Understanding emerging and re-emerging viruses to facilitate pandemic preparedness","authors":"Francisco J. Zapatero-Belinchón, Priti Kumar, Melanie Ott, Olivier Schwartz, Alex Sigal","doi":"10.1038/s41564-024-01789-5","DOIUrl":"10.1038/s41564-024-01789-5","url":null,"abstract":"On 8–11 April 2024, a Keystone meeting on human immunodeficiency virus and emerging and re-emerging viruses convened in Hannover, Germany, aiming to unite researchers studying viruses of global concern, and gain a deep understanding of unique and shared viral disease mechanisms to facilitate pandemic preparedness.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2208-2211"},"PeriodicalIF":20.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085510","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
Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation 曲霉分生孢子表面相关蛋白质组揭示了真菌逃避和宿主免疫调节的因素。
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-27 DOI: 10.1038/s41564-024-01782-y
Camila Figueiredo Pinzan, Clara Valero, Patrícia Alves de Castro, Jefferson Luiz da Silva, Kayleigh Earle, Hong Liu, Maria Augusta Crivelente Horta, Olaf Kniemeyer, Thomas Krüger, Annica Pschibul, Derya Nur Cömert, Thorsten Heinekamp, Axel A. Brakhage, Jacob L. Steenwyk, Matthew E. Mead, Nico Hermsdorf, Scott G. Filler, Nathalia Gonsales da Rosa-Garzon, Endrews Delbaje, Michael J. Bromley, Hamilton Cabral, Camila Diehl, Claudia B. Angeli, Giuseppe Palmisano, Ashraf S. Ibrahim, David C. Rinker, Thomas J. C. Sauters, Karin Steffen, Adiyantara Gumilang, Antonis Rokas, Sara Gago, Thaila F. dos Reis, Gustavo H. Goldman
{"title":"Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation","authors":"Camila Figueiredo Pinzan, Clara Valero, Patrícia Alves de Castro, Jefferson Luiz da Silva, Kayleigh Earle, Hong Liu, Maria Augusta Crivelente Horta, Olaf Kniemeyer, Thomas Krüger, Annica Pschibul, Derya Nur Cömert, Thorsten Heinekamp, Axel A. Brakhage, Jacob L. Steenwyk, Matthew E. Mead, Nico Hermsdorf, Scott G. Filler, Nathalia Gonsales da Rosa-Garzon, Endrews Delbaje, Michael J. Bromley, Hamilton Cabral, Camila Diehl, Claudia B. Angeli, Giuseppe Palmisano, Ashraf S. Ibrahim, David C. Rinker, Thomas J. C. Sauters, Karin Steffen, Adiyantara Gumilang, Antonis Rokas, Sara Gago, Thaila F. dos Reis, Gustavo H. Goldman","doi":"10.1038/s41564-024-01782-y","DOIUrl":"10.1038/s41564-024-01782-y","url":null,"abstract":"Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection. Analysis of the conidial surface proteome of the fungal pathogen Aspergillus fumigatus and three closely related species reveals factors important for evasion and modulation of host immunity","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2710-2726"},"PeriodicalIF":20.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081007","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
Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities 真菌病原体对宿主吞噬功能的操纵和治疗机会。
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-26 DOI: 10.1038/s41564-024-01780-0
Lei-Jie Jia, Katherine González, Thomas Orasch, Franziska Schmidt, Axel A. Brakhage
{"title":"Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities","authors":"Lei-Jie Jia, Katherine González, Thomas Orasch, Franziska Schmidt, Axel A. Brakhage","doi":"10.1038/s41564-024-01780-0","DOIUrl":"10.1038/s41564-024-01780-0","url":null,"abstract":"An important host defence mechanism against pathogens is intracellular killing, which is achieved through phagocytosis, a cellular process for engulfing and neutralizing extracellular particles. Phagocytosis results in the formation of matured phagolysosomes, which are specialized compartments that provide a hostile environment and are considered the end point of the degradative pathway. However, all fungal pathogens studied to date have developed strategies to manipulate phagosomal function directly and also indirectly by redirecting phagosomes from the degradative pathway to a non-degradative pathway with the expulsion and even transfer of pathogens between cells. Here, using the major human fungal pathogens Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum as examples, we discuss the processes involved in host phagosome–fungal pathogen interactions, with a focus on fungal evasion strategies. We also discuss recent approaches to targeting intraphagosomal pathogens, including the redirection of phagosomes towards degradative pathways for fungal pathogen eradication. In this Review, the authors discuss fungal pathogen–host interactions with a focus on phagocytosis and intracellular processing of pathogens within phagosomes. They also outline potential therapeutic approaches for targeting intraphagosomal pathogens.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2216-2231"},"PeriodicalIF":20.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073306","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
Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification SARS-CoV-2 在小鼠中枢神经系统中的进化推动了病毒的多样化
IF 20.5 1区 生物学
Nature Microbiology Pub Date : 2024-08-23 DOI: 10.1038/s41564-024-01786-8
Jacob Class, Lacy M. Simons, Ramon Lorenzo-Redondo, Jazmin Galván Achi, Laura Cooper, Tanushree Dangi, Pablo Penaloza-MacMaster, Egon A. Ozer, Sarah E. Lutz, Lijun Rong, Judd F. Hultquist, Justin M. Richner
{"title":"Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification","authors":"Jacob Class, Lacy M. Simons, Ramon Lorenzo-Redondo, Jazmin Galván Achi, Laura Cooper, Tanushree Dangi, Pablo Penaloza-MacMaster, Egon A. Ozer, Sarah E. Lutz, Lijun Rong, Judd F. Hultquist, Justin M. Richner","doi":"10.1038/s41564-024-01786-8","DOIUrl":"10.1038/s41564-024-01786-8","url":null,"abstract":"Severe coronavirus disease 2019 and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with neurological complications that may be linked to direct infection of the central nervous system (CNS), but the selective pressures ruling neuroinvasion are poorly defined. Here we assessed SARS-CoV-2 evolution in the lung versus CNS of infected mice. Higher levels of viral divergence were observed in the CNS than the lung after intranasal challenge with a high frequency of mutations in the spike furin cleavage site (FCS). Deletion of the FCS significantly attenuated virulence after intranasal challenge, with lower viral titres and decreased morbidity compared with the wild-type virus. Intracranial inoculation of the FCS-deleted virus, however, was sufficient to restore virulence. After intracranial inoculation, both viruses established infection in the lung, but dissemination from the CNS to the lung required the intact FCS. Cumulatively, these data suggest a critical role for the FCS in determining SARS-CoV-2 tropism and compartmentalization. SARS-CoV-2 replication in the murine lung requires the spike furin cleavage site, which is then lost during divergence in the brain.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2383-2394"},"PeriodicalIF":20.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042608","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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