iScience最新文献_第9页

Urine metabolomic analyses reveal metabolite disruptions in steroid hormone biosynthesis in monkeypox 尿代谢组学分析揭示猴痘中类固醇激素生物合成的代谢物中断

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-29 DOI: 10.1016/j.isci.2025.112554

Xiaofeng Yang , Huiqin Yang , Chudan Liang , Fei Tang , Zhenyu Long , Linjin Fan , Yulong Wang , Zequn Wang , Mou Zeng , Weifang Kang , Pengfei Ye , Wendi Shi , Yuandong Zhou , Jingyan Lin , Hongxin Huang , Huijun Yan , Jian Wang , Linghua Li , Jun Qian , Linna Liu

{"title":"Urine metabolomic analyses reveal metabolite disruptions in steroid hormone biosynthesis in monkeypox","authors":"Xiaofeng Yang , Huiqin Yang , Chudan Liang , Fei Tang , Zhenyu Long , Linjin Fan , Yulong Wang , Zequn Wang , Mou Zeng , Weifang Kang , Pengfei Ye , Wendi Shi , Yuandong Zhou , Jingyan Lin , Hongxin Huang , Huijun Yan , Jian Wang , Linghua Li , Jun Qian , Linna Liu","doi":"10.1016/j.isci.2025.112554","DOIUrl":"10.1016/j.isci.2025.112554","url":null,"abstract":"<div><div>Monkeypox virus (MPXV) poses a global health threat. Viral infection can alter host metabolic homeostasis, while its changes may influence disease severity and progression. The relationship between MPXV and metabolites has not been reported. we employed metabolomics to characterize the mpox specific metabolic features by comparing changes in urinary metabolites from patients with MPXV infection, HIV infection, and HIV-MPXV co-infection. The metabolic changes caused by MPXV were mainly concentrated in amino acid and hormone metabolism. Further analysis showed that 5′-dihydroadenosine and uric acid can serve as potential molecular markers for MPXV and HIV-MPXV co-infected patients, respectively. Confirmed by targeted metabolomics and ELISA methods, MPXV infection caused severe disorders in the metabolic pathways of steroid hormones such as testosterone and progesterone in humans. Our findings identify dysregulated metabolism as an underpinning of MPXV pathogenicity, and increasing the anti-inflammatory capacity of patients may play a role to some extent against mpox.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112554"},"PeriodicalIF":4.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive benchmarking of genome editing quantification methods for plant applications 植物基因组编辑量化方法的综合标杆分析

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-29 DOI: 10.1016/j.isci.2025.112350

Zheng Gong (龚政) , Yan Zhang (张妍) , Di Xia , Sohye Yoon , Peter Alexander Crisp , José Ramón Botella

{"title":"Comprehensive benchmarking of genome editing quantification methods for plant applications","authors":"Zheng Gong (龚政) , Yan Zhang (张妍) , Di Xia , Sohye Yoon , Peter Alexander Crisp , José Ramón Botella","doi":"10.1016/j.isci.2025.112350","DOIUrl":"10.1016/j.isci.2025.112350","url":null,"abstract":"<div><div>Accurately detecting and quantifying CRISPR edits with high sensitivity is crucial for developing new genome editing applications in plants. This is especially important when analyzing heterogeneous populations from transient expression-based approaches used for technology development as well as evaluating of guide RNA (gRNA) performance <em>in planta</em>. However, current studies employ vastly different techniques to quantify genome editing outcomes, limiting the comparability and repeatability of results. In this study, we systematically evaluated and compared experimental techniques for quantifying plant genome editing across a wide range of efficiencies. We measured genome editing efficiency from 20 transiently expressed Cas9 targets using different techniques, including targeted amplicon sequencing (AmpSeq), PCR-restriction fragment length polymorphism (RFLP) assays, T7 endonuclease 1 (T7E1) assays, Sanger sequencing of amplicon products (deconvoluted and analyzed using three algorithms), PCR-capillary electrophoresis/InDel detection by amplicon analysis (PCR-CE/IDAA), and droplet digital PCR (ddPCR). We assessed methods based on their accuracy, sensitivity, and cost, benchmarked to AmpSeq. Furthermore, we discuss the advantages and drawbacks of each technique, the issues faced during optimization and the solutions we devised. This study will be useful to experienced and new researchers in the field, providing suggestions and guidelines to standardize data output and advice about the most suitable technique/s to quantify genome edits for different plant applications.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112350"},"PeriodicalIF":4.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimal dynamic soaring trades off energy harvest and directional flight 最优动态飞行权衡了能量收集和定向飞行

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112540

Lunbing Chen , Yufei Yin , Yang Xiang , Suyang Qin , Hong Liu

{"title":"Optimal dynamic soaring trades off energy harvest and directional flight","authors":"Lunbing Chen , Yufei Yin , Yang Xiang , Suyang Qin , Hong Liu","doi":"10.1016/j.isci.2025.112540","DOIUrl":"10.1016/j.isci.2025.112540","url":null,"abstract":"<div><div>Wandering albatrosses use dynamic soaring to achieve low-cost, continuous flight over thousands of kilometers. While previous research has primarily focused on energy harvest, directional flight may be more important for reaching a destination. Through numerical simulations validated by flight tracking data, this study reveals a trade-off between maximizing energy harvest and achieving the fastest directional progress: maximizing energy gain increases mechanical energy but slows target-oriented movement, while prioritizing directional flight reduces energy gain. Albatrosses balance this trade-off through a step-selection strategy, dividing each flight cycle into energy-harvest and directional-flight phases, each with distinct priorities. The duration of each phase is influenced by environmental shear strength: low-shear conditions allocate more time to harvest energy, while high-shear conditions favor faster directional movement. By optimizing this balance, albatrosses achieve efficient destination-oriented soaring. These insights enhance our understanding of pelagic bird flight and could inspire high-efficiency robotic albatrosses.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112540"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selective emotion regulation in creative art production: Psychophysiological reactivity during painting reduces anxiety 创造性艺术生产中的选择性情绪调节：绘画中的心理生理反应减少焦虑

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112543

Lucas Bellaiche , Kayla Lihardo , Chloe Williams , Jill Chaffee , Kevin S. LaBar , Paul Seli

{"title":"Selective emotion regulation in creative art production: Psychophysiological reactivity during painting reduces anxiety","authors":"Lucas Bellaiche , Kayla Lihardo , Chloe Williams , Jill Chaffee , Kevin S. LaBar , Paul Seli","doi":"10.1016/j.isci.2025.112543","DOIUrl":"10.1016/j.isci.2025.112543","url":null,"abstract":"<div><div>Across the literatures of aesthetics, philosophy, and psychology, art has long been revered as a powerful means to enhance mental well-being—a perspective that has been integrated into clinical practices worldwide. While some empirical research supports the emotional benefits of art production, such work often captures non-creativity factors (e.g., physical movement and social interaction), leaving the contribution of creative expression on psychophysiological outcomes unclear. To address this issue, we conducted a pre-registered, multi-modal, repeated-measures study wherein participants completed both a painting task and a non-creative but active control task. Our findings demonstrate that, above and beyond the non-creativity processes shared with the control task, painting selectively reduces anxiety, and that greater cognitive engagement and physiological reactivity characterize this reduction. These findings highlight the multi-modal determinants of emotional improvement during artistic production, providing empirical support for the therapeutic benefits of art-making specific to the regulation of anxiety.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112543"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Locus-specific human endogenous retroviruses reveal lymphoma subtypes 基因座特异性人类内源性逆转录病毒揭示淋巴瘤亚型

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112541

Bhavya Singh , Nicholas Dopkins , Tongyi Fei , Jez L. Marston , Stephanie Michael , Helena Reyes-Gopar , Gislaine Curty , Jonas J. Heymann , Amy Chadburn , Peter Martin , Fabio E. Leal , Ethel Cesarman , Douglas F. Nixon , Matthew L. Bendall

{"title":"Locus-specific human endogenous retroviruses reveal lymphoma subtypes","authors":"Bhavya Singh , Nicholas Dopkins , Tongyi Fei , Jez L. Marston , Stephanie Michael , Helena Reyes-Gopar , Gislaine Curty , Jonas J. Heymann , Amy Chadburn , Peter Martin , Fabio E. Leal , Ethel Cesarman , Douglas F. Nixon , Matthew L. Bendall","doi":"10.1016/j.isci.2025.112541","DOIUrl":"10.1016/j.isci.2025.112541","url":null,"abstract":"<div><div>The heterogeneity of cancers is driven by diverse mechanisms underlying oncogenesis such as differential ‘cell-of-origin’ progenitors, mutagenesis, and viral infections. Classification of B cell lymphomas has been defined by considering these characteristics. However, the expression and contribution of endogenous retroelements (EREs) to B cell lymphoma oncogenesis or classification have been overlooked. We hypothesized that incorporating ERE expression signatures would increase the resolution of B cell identity during healthy and malignant conditions. Here, we present the first comprehensive, locus-specific characterization of ERE expression in benign germinal center B cells, diffuse large B cell lymphoma, Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma, and follicular lymphoma. Our findings demonstrate unique human ERE signatures in the GC and lymphoma subtypes whose activity can be used in combination with gene expression to define B cell lineage in lymphoid malignancies, highlighting the potential of ERE analyses as a tool in lymphoma classification, diagnosis, and the identification of treatment groups.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112541"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress 鼠李糖乳杆菌衍生的细胞外囊泡影响乳腺癌导管内钙应激模型中的钙沉积

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112538

Ngoc Vuong , Melany Alomia , Ahana Byne , Purva Gade , Thomas Raymond Philipson , Rayan Ibrahim Alhammad , Cade J. Skislak , Intisar Alruwaili , Fahad M. Alsaab , Weidong Zhou , Marissa Howard , Andrea Brothers , Amanda Haymond Still , Robyn P. Araujo , Monique Van Hoek , Barbara Birkaya , Virginia Espina , Richard A. Hoefer , Lance Liotta , Alessandra Luchini

{"title":"Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress","authors":"Ngoc Vuong , Melany Alomia , Ahana Byne , Purva Gade , Thomas Raymond Philipson , Rayan Ibrahim Alhammad , Cade J. Skislak , Intisar Alruwaili , Fahad M. Alsaab , Weidong Zhou , Marissa Howard , Andrea Brothers , Amanda Haymond Still , Robyn P. Araujo , Monique Van Hoek , Barbara Birkaya , Virginia Espina , Richard A. Hoefer , Lance Liotta , Alessandra Luchini","doi":"10.1016/j.isci.2025.112538","DOIUrl":"10.1016/j.isci.2025.112538","url":null,"abstract":"<div><div>Extracellular calcium export by the breast ductal epithelium is crucial during lactation and plays a significant role in breast cancer progression. Intraductal calcium deposition is a hallmark of aggressive premalignant lesions. This study tested the hypothesis that microbiome-derived extracellular vesicles (EVs) influence calcium modulation in premalignant breast cancer lesions. Based on the analysis of plasma, serum, saliva, and tissue collected from breast cancer patients and controls (<em>N</em> = 150), <em>Lactobacillus rhamnosus</em> (<em>Lr</em>) was chosen as the model microbiota. In a BT-474 human breast cancer cell line monolayer culture under acute calcium stress, <em>Lr</em> EVs enhanced intracellular calcium intake. In a BT474 3D spheroid model under chronic calcium stress, <em>Lr</em> EVs increased extracellular calcium deposition and mRNA expression of calcium export channel plasma membrane calcium-transporting ATPase 2 (PMCA2) and stromal interaction molecule 1 (STIM1) in a dose-dependent manner. We propose that <em>Lr</em> EVs influence calcium regulation and mineral deposition, thereby affecting premalignant breast cancer progression.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112538"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Compact waveguide-integrated metasurface twist with filtering and phase shifting capabilities for millimeter-wave guided-wave applications 紧凑型波导集成超表面扭曲与滤波和移相能力，毫米波导波应用

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112479

Amirmasood Bagheri , Zahra Rahimian Omam , Pei Xiao , Seyed Ehsan Hosseininejad , Mohsen Khalily

{"title":"Compact waveguide-integrated metasurface twist with filtering and phase shifting capabilities for millimeter-wave guided-wave applications","authors":"Amirmasood Bagheri , Zahra Rahimian Omam , Pei Xiao , Seyed Ehsan Hosseininejad , Mohsen Khalily","doi":"10.1016/j.isci.2025.112479","DOIUrl":"10.1016/j.isci.2025.112479","url":null,"abstract":"<div><div>Recent advancements in metasurfaces have enabled precise control of wave properties such as amplitude, phase, and polarization, which are critical for multifunctional devices in modern communications. While most metasurfaces are designed for free-space use, this work integrates metasurfaces within waveguides to enable guided-wave control. We introduce a compact waveguide-integrated metasurface twist that achieves polarization rotation, bandpass filtering, and phase shifting. The metasurface comprises a <span><math><mrow><mn>3</mn><mo>×</mo><mn>3</mn></mrow></math></span> array of dog bone–shaped resonators and orthogonal gratings. Positioned between two rectangular waveguides with a <span><math><mrow><mn>90</mn><mo>°</mo></mrow></math></span> twist, it allows precise tuning of wave properties. A fabricated prototype operating in the 26.6–29 GHz band shows an average insertion loss of 0.6 dB and a minimum of 0.34 dB at 28 GHz. This work demonstrates a compact, high-performance solution for millimeter-wave (mm-wave) guided-wave systems with a device thickness of only <span><math><mrow><mn>0.16</mn><msub><mi>λ</mi><mi>g</mi></msub></mrow></math></span>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112479"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Covalent inhibition of Plasmodium falciparum Ubc13 impairs global protein synthesis 恶性疟原虫Ubc13共价抑制损害了全球蛋白合成

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112545

Anna Truong , Ruitian Hu , Baiyi Quan , Morgan A. Bailey , Erin A. Schroeder , Kayla Sylvester , Gaëlle Neveu , Björn F.C. Kafsack , Michael C. Fitzgerald , Emily R. Derbyshire

{"title":"Covalent inhibition of Plasmodium falciparum Ubc13 impairs global protein synthesis","authors":"Anna Truong , Ruitian Hu , Baiyi Quan , Morgan A. Bailey , Erin A. Schroeder , Kayla Sylvester , Gaëlle Neveu , Björn F.C. Kafsack , Michael C. Fitzgerald , Emily R. Derbyshire","doi":"10.1016/j.isci.2025.112545","DOIUrl":"10.1016/j.isci.2025.112545","url":null,"abstract":"<div><div>The ubiquitin-conjugating enzyme 13 (Ubc13) has an essential function and putative role in artemisinin activity against <em>Plasmodium falciparum</em>. Ubc13 conjugates lysine 63-linked ubiquitin (K63-Ub) to proteins, but the role of this modification in <em>Plasmodium</em> remains largely unknown. Herein, we characterize and deploy NSC697923 to interrogate PfUbc13 function. We demonstrate that NSC697923 covalently targets the PfUbc13 catalytic cysteine and exhibits nanomolar inhibitory potency. NSC697923 inhibits multiple life stages and synergizes with the malaria drug dihydroartemisinin. NSC697923 specifically reduces K63-Ub in blood stage parasites, and subsequent chemoproteomic studies identified 31 putative PfUbc13 substrates. These proteins were enriched in transcription, translation, and proteasome processes, and 90% overlapped with previous <em>Plasmodium</em> ubiquitinome studies. Nascent protein synthesis was reduced following NSC697923 exposure, supporting a role for PfUbc13 and K63-Ub in mediating protein translation. These findings expand our knowledge of PfUbc13-dependent processes in these pathogenic parasites and highlight this enzyme as a potential antimalarial drug target.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112545"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a peptide-based vaccine using a T cell epitope derived from SARS-CoV-2 基于SARS-CoV-2衍生的T细胞表位的肽基疫苗的开发

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112542

Satoshi Baba , Hiroki Hayashi , Shota Yoshida , Nanxiang Yin , Munehisa Shimamura , Ryuichi Morishita , Hiromi Rakugi , Hironori Nakagami , Koichi Yamamoto

{"title":"Development of a peptide-based vaccine using a T cell epitope derived from SARS-CoV-2","authors":"Satoshi Baba , Hiroki Hayashi , Shota Yoshida , Nanxiang Yin , Munehisa Shimamura , Ryuichi Morishita , Hiromi Rakugi , Hironori Nakagami , Koichi Yamamoto","doi":"10.1016/j.isci.2025.112542","DOIUrl":"10.1016/j.isci.2025.112542","url":null,"abstract":"<div><div>Follicular helper T (Tfh) cells are a subset of CD4<sup>+</sup> T cells that help B cells to produce high-affinity antibodies. Efficient Tfh cell induction by vaccines is critical for protective efficacy against diseases. A Tfh epitope, identified from the SARS-CoV-2 spike protein, has been shown to bind to the corresponding HLA and activates Tfh cells. Here, we assessed the efficacy of a peptide vaccine conjugated with SARS-CoV-2 Tfh epitope against experimental hypertension in a mouse model. The Tfh-angiotensin II (Tfh-Ang II) vaccine activated Tfh and germinal center B cells and induced antibodies against Ang II, thereby suppressing hypertension. However, Ang II-specific autoreactive T cells were not induced. Interestingly, Tfh-Ang II-induced antibody production was enhanced by SARS-CoV-2 spike priming. Moreover, human peripheral blood mononuclear cells from individuals vaccinated with COVID-19 mRNA vaccine were activated by Tfh epitope. Collectively, the SARS-CoV-2 spike-derived universal Tfh epitope may be effective for peptide-based vaccine development.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112542"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STT3A-mediated mega protein complex assembly during dengue and Zika virus infection 登革热和寨卡病毒感染过程中stt3a介导的巨量蛋白复合物组装

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-28 DOI: 10.1016/j.isci.2025.112535

Tao Liu , Natasha W. Hanners , Huangheng Tao , Claudia Szabo , Dao Xu , Wei Lin , John W. Schoggins , Nan Yan , Jianjun Wu

{"title":"STT3A-mediated mega protein complex assembly during dengue and Zika virus infection","authors":"Tao Liu , Natasha W. Hanners , Huangheng Tao , Claudia Szabo , Dao Xu , Wei Lin , John W. Schoggins , Nan Yan , Jianjun Wu","doi":"10.1016/j.isci.2025.112535","DOIUrl":"10.1016/j.isci.2025.112535","url":null,"abstract":"<div><div>Flavivirus replication in mammalian cells requires host oligosaccharyltransferase (OST) complex, which is classically known to catalyze protein N-glycosylation. However, enzymatic activity of OST is not required for flavivirus infection, leaving the underlying mechanism puzzling. We show the STT3A sub-complex of OST, including STT3A and DC2, to be critically required for dengue virus (DENV) and Zika virus (ZIKV) infection. We find that STT3A nucleates a mega protein complex assembly during DENV infection as a scaffold through its interaction with other OST subunits, translocon proteins, and viral nonstructural proteins. The integrity of this mega protein complex is important for supporting flavivirus infection. We also identified a small-molecule compound NSC-323241 that disrupts STT3A-mediated mega protein complex assembly and potently blocks DENV and ZIKV infection. Together, our study reveals a scaffolding function of STT3A in flavivirus infection through comprehensive molecular dissection of the multi-subunit OST complex and associated host and viral proteins.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112535"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0