BMC Biology最新文献

{"title":"DTI-RME: a robust and multi-kernel ensemble approach for drug-target interaction prediction.","authors":"Yuqing Qian, Xin Zhang, Yizheng Wang, Quan Zou, Chen Cao, Yijie Ding, Xiaoyi Guo","doi":"10.1186/s12915-025-02340-6","DOIUrl":"10.1186/s12915-025-02340-6","url":null,"abstract":"<p><strong>Background: </strong>Drug-target interaction (DTI) refers to the specific mechanisms by which drug molecules interact with biological targets within a biological system. Computational methods are widely employed for DTI prediction, as they are time-efficient and resource-saving compared to experimental approaches. Although numerous DTI prediction methods have achieved promising results, accurately modeling DTIs remains challenging due to three key issues: noisy interaction labels, ineffective multi-view fusion, and incomplete structural modeling.</p><p><strong>Results: </strong>We propose a novel method termed DTI-RME. The DTI-RME introduces an innovative <math> <mrow><msub><mi>L</mi> <mn>2</mn></msub> <mo>-</mo> <mi>C</mi></mrow> </math> loss function that combines the benefits of <math><msub><mi>L</mi> <mn>2</mn></msub> </math> loss to reduce prediction errors and the robustness of C-loss in handling outliers. This method fuses multiple views through multi-kernel learning that assigns weights to different kernels. DTI-RME uses ensemble learning to assume and learn multiple structures, including the drug-target pair, drug, target, and low-rank structures.</p><p><strong>Conclusions: </strong>We evaluated DTI-RME on five real-world DTI datasets and conducted experiments focusing on three key scenarios. In all experiments, DTI-RME demonstrated superior performance compared to existing methods. Furthermore, the case study confirmed DTI-RME's ability to identify novel drug-target interactions accurately, with 17 of the top 50 predicted interactions being validated.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"225"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728081","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}

{"title":"Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes.","authors":"Elodie Couderc, Anna B Crist, Josquin Daron, Hugo Varet, Femke A H van Hout, Pascal Miesen, Umberto Palatini, Stéphanie Dabo, Thomas Vial, Louis Lambrechts, Sarah H Merkling","doi":"10.1186/s12915-025-02325-5","DOIUrl":"10.1186/s12915-025-02325-5","url":null,"abstract":"<p><strong>Background: </strong>Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown.</p><p><strong>Results: </strong>We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito's body was slightly impaired, albeit not altering virus transmission rates.</p><p><strong>Conclusions: </strong>Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"223"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728079","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}

{"title":"Universal orthologs infer deep phylogenies and improve genome quality assessments.","authors":"Md Nafis Ul Alam, Cristian Román-Palacios, Dario Copetti, Rod A Wing","doi":"10.1186/s12915-025-02328-2","DOIUrl":"10.1186/s12915-025-02328-2","url":null,"abstract":"<p><strong>Background: </strong>Universal single-copy orthologs are the most conserved components of genomes. Although they are routinely used for studying evolutionary histories and assessing new assemblies, current methods do not incorporate information from available genomic data.</p><p><strong>Results: </strong>Here, we first determine the influence of evolutionary history on universal gene content and find that across 11,098 genomes of plants, fungi, and animals comprising 2606 taxonomic groups, 215 groups significantly vary from their respective lineages in terms of BUSCO (Benchmarking Universal Single Copy Orthologs) completeness. Additionally, 169 groups display an elevated complement of duplicated orthologs, likely from ancestral whole genome duplication events. Secondly, we investigate the extent of taxonomic congruence in broad BUSCO-derived phylogenies. For 275 suitable families out of 543 tested, sites evolving at higher rates produce at most 23.84% more taxonomically concordant, and at least 46.15% less terminally variable phylogenies compared to lower-rate sites. We find that BUSCO concatenated and coalescent trees have comparable accuracy and conclude that higher rate sites from concatenated alignments produce the most congruent and least variable phylogenies. Finally, we show that undetected, yet pervasive BUSCO gene loss events lead to misrepresentations of assembly quality. To overcome this, we filter a Curated set of BUSCOs (CUSCOs) that provide up to 6.99% fewer false positives compared to the standard search and introduce novel methods for comparing assemblies using gene synteny.</p><p><strong>Conclusions: </strong>Overall, we highlight the importance of considering evolutionary histories during assembly evaluations and release the phyca software toolkit that reconstructs consistent phylogenies and offers more precise assembly assessments.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"224"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728085","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}

{"title":"An ovarian insulin-like peptide specifically regulates energy allocation and oocyte development in nutrition-restricted cockroaches.","authors":"Yuan Luo, Wen-Xin Hou, Shan-Shan Zhao, Yun-Long Cheng, Ke-Jia Zhang, Liang-Guan Lin, Sheng Li, Xiao-Jin Pei","doi":"10.1186/s12915-025-02342-4","DOIUrl":"10.1186/s12915-025-02342-4","url":null,"abstract":"<p><strong>Background: </strong>Insects exhibit remarkable resilience and maintain high levels of reproduction despite frequently encountering nutritional restriction. However, the mechanisms governing their adaptive reproductive strategies under nutrition-restricted conditions remain poorly understood. The German cockroach Blattella germanica, a widespread urban pest, exhibits remarkable reproductive capabilities even in domestic environments where food resources are frequently limited.</p><p><strong>Results: </strong>In this study, we demonstrate that the ovary plays a crucial role in promoting vitellogenin biosynthesis and oocyte development under nutrition-restricted conditions through hemiovariectomy. Employing transcriptome analysis, RNAi screening, and fluorescence in situ hybridization, we identified an ovarian-enriched insulin-like peptide gene (BgILP2) that is dramatically upregulated during low nutrition conditions. Repression of BgILP2 impairs vitellogenesis in the fat body through downregulation of p-AKT and p-ERK levels while simultaneously disrupting juvenile hormone synthesis, ultimately leading to delayed oocyte development under nutrient restriction. Furthermore, under low-nutrient conditions, repression of BgILP2 led to elevated circulating sugar levels, reduced lipid and glycogen storage, and a modest increase in the lifespan of female cockroaches.</p><p><strong>Conclusions: </strong>The ovarian-enriched BgILP2 responds to nutritional stress and activates the insulin signaling pathway to sustain oocyte development under nutrient-restricted conditions. Furthermore, BgILP2 mediates energy allocation and prioritizes reproductive investment potentially at the expense of longevity, which reflects a tradeoff between reproduction and somatic maintenance under nutrient restriction. These findings provide novel insights into the molecular mechanisms and adaptive strategies that enable cockroaches to maintain reproductive success in food-limited environments.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"226"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728080","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}

{"title":"Integration of pre-trained protein language models with equivariant graph neural networks for peptide toxicity prediction.","authors":"Shihu Jiao, Xiucai Ye, Tetsuya Sakurai, Quan Zou, Wu Han, Chao Zhan","doi":"10.1186/s12915-025-02329-1","DOIUrl":"10.1186/s12915-025-02329-1","url":null,"abstract":"<p><strong>Background: </strong>Peptide-based therapeutics have great potential due to their versatility, high specificity, and suitability for a variety of therapeutic applications. Despite these advantages, the inherent toxicities of some peptides pose challenges in drug development. Several computational methods have been developed to allow rapid and efficient large-scale screening of peptide toxicity. However, these methods mainly rely on the primary sequence and often ignore critical structural information, which limits their predictive accuracy.</p><p><strong>Results: </strong>In this study, we introduce a novel framework named StrucToxNet that integrates a pre-trained protein language model with an equivariant graph neural network to improve peptide toxicity prediction. By combining sequence embeddings from the ProtT5 language model and 3D structural data predicted by ESMFold, StrucToxNet can capture both sequential and spatial characteristics of peptides. Testing on the independent dataset indicates that StrucToxNet outperforms existing sequence-based models in various metrics, achieving higher balanced accuracy and overall performance.</p><p><strong>Conclusions: </strong>The results demonstrate the robustness and generalizability of StrucToxNet, marking it a reliable tool in the computational screening of toxic peptides and facilitating safer peptide-based drug development.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"229"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728083","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}

{"title":"Ephaptic conduction molding memory engrams.","authors":"A Rabinovitch, R Rabinovitch, D Braunstein, E Smolik, Y Biton","doi":"10.1186/s12915-025-02323-7","DOIUrl":"10.1186/s12915-025-02323-7","url":null,"abstract":"<p><strong>Background: </strong>Memories are programmed in the brain as connected neuronal ensembles called engrams. However, the method by which the brain forms engrams during memory encoding is not understood.</p><p><strong>Results: </strong>We have created a mechanistic mathematical model showing a possible method of the encoding process. Our model is based on the cellular automata approach, which can specifically distinguish between neurons operated on by the synaptic and those operated on by the ephaptic modes. This feature allows us to confirm that the ephaptic mode induces the formation of repeating collections of operating neurons (sub-engrams) that can become memory-preserving entities, and the synaptic influence is manifested by molding these sub-engrams by pruning small ones and size-increasing and rounding larger ones to form the engrams' final structures.</p><p><strong>Conclusions: </strong>Ephaptic and synaptic dual-participation in the memory encoding process was exhibited. The sequence of activities was unveiled. We also speculate on possible procedures the brain can employ to enable the ephaptic mode to overtake the normal, synaptic-dominating one.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"221"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688898","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}

{"title":"Wide-scale geographical analysis of genetic ancestry in the South African Coloured population.","authors":"Imke Lankheet, Rickard Hammarén, Lucía Ximena Alva Caballero, Maximilian Larena, Helena Malmström, Cecile Jolly, Himla Soodyall, Michael de Jongh, Carina Schlebusch","doi":"10.1186/s12915-025-02317-5","DOIUrl":"10.1186/s12915-025-02317-5","url":null,"abstract":"<p><strong>Background: </strong>The South African Coloured (SAC) population, a prominent admixed population in South Africa, reflects centuries of migration, admixture, and historical segregation. Descendants of local Khoe-San and Bantu-speaking populations, European settlers, and enslaved individuals from Africa and Asia, SAC individuals embody diverse ancestries. This study investigates the genetic makeup of SAC individuals, utilizing autosomal genotypes, mitochondrial DNA and Y-chromosome data. We analyse new genotype data for 125 SAC individuals from seven locations.</p><p><strong>Results: </strong>Our analysis, based on a dataset comprising 356 SAC individuals from 22 geographic locations, revealed significant regional variations in ancestry. Khoe-San ancestry predominates in 14 locations, highlighting its lasting influence. Inland regions exhibit higher proportions of Khoe-San ancestry, eastern regions show more Bantu-speaker/West African ancestry, and western/coastal areas, particularly around Cape Town, display increased Asian ancestry. Additionally, sex-biased admixture ratios show male-biased admixture from East Africans and Europeans, and female-biased admixture from Khoe-San populations, which is supported by mitochondrial and Y-chromosome data.</p><p><strong>Conclusions: </strong>The observed patterns of significant regional variation in ancestry reflect historical migrations and settlement patterns. This research underscores the importance of studying the SAC population to understand South Africa's historical migrations, providing insights into the complex genetic heritage of South Africans.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"219"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688900","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}

{"title":"Resource reallocation under persistent immune activation drives trade-offs between life history and immunity in pirk-deficient Musca domestica.","authors":"Ting Tang, Lan Yang, Liya Ma, Yu Ren, Mengnan Li, Shufan Guo, Xin Wang, Yuming Zhang, Fengsong Liu","doi":"10.1186/s12915-025-02324-6","DOIUrl":"10.1186/s12915-025-02324-6","url":null,"abstract":"<p><strong>Background: </strong>The activation of the immune system by pathogens imposes significant energetic costs on hosts, which may result in the diversion of resources away from other non-essential biological processes, such as growth and reproduction. The underlying mechanisms of trade-offs between immune responses and host fitness remain poorly understood.</p><p><strong>Results: </strong>We used a Musca domestica mutant (pirk-KO) to evaluate the influence of non-infection-induced immune system activation on female reproduction and larval growth. Pirk, a negative feedback inhibitor of the immune deficiency (Imd) pathway expressed in intestine and fat body, was induced by bacteria. pirk loss enhanced the immune response of house flies, reflected in sustained upregulated antimicrobial peptide gene expression and improved resistance to bacterial infections. The phenotypic traits of pirk-KO house flies, including delayed larval growth, reduced the body weight, and impaired female fertility, were indicative of the adaptive costs associated with aberrant immune activation. The transcriptional heterogeneities between pirk-KO and wild-type (WT) male flies indicated the overactivation of the Imd signaling pathway, accompanied by significant metabolic adaptations to the loss of pirk. The upregulation of pivotal genes involved in glycolysis and the TCA cycle indicated an enhanced central carbon metabolism in pirk-KO. The downregulation of multiple key enzymes involved in the pentose phosphate pathway in pirk-KO flies suggests a reduction in metabolic flux through the pentose phosphate pathway, which in turn results in impaired anabolism. The collective findings indicate that the pirk-KO flies undergo metabolic reprogramming to increase ATP production as a response to excessive immune activation, rather than incorporating nutrients into cellular biomass for cell proliferation. The pirk-KO flies exhibited a significantly elevated food intake and elevated levels of free glucose, trehalose, and fructose in comparison to the WT flies. Nevertheless, the glycogen and triglyceride contents in the pirk-KO flies were observed to be slightly diminished in comparison to the WT group.</p><p><strong>Conclusions: </strong>When the immune defense is activated, the flies extract more free energy to fuel the immunological deployment by increasing nutrient intake, as well as reducing resource allocation to non-essential life-history traits, primarily reproduction and growth.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"220"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688899","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}

{"title":"Decidual stromal cells-derived exosomes incured insufficient migration and invasion of trophoblast because of abnormal ubiquitination and degradation of Snail mediated by miR-92b-3p/USP28.","authors":"Miao Xiong, Ziqiu He, Liping Wen, Aimin Zhao","doi":"10.1186/s12915-025-02326-4","DOIUrl":"10.1186/s12915-025-02326-4","url":null,"abstract":"<p><strong>Background: </strong>Recent findings have demonstrated that inadequate trophoblast migration and invasion are often responsible for the unsuccessful communication between the mother and fetus, contributing to URSA (unexplained recurrent spontaneous abortion). Effective intercellular communication at the maternal-fetal interface is crucial for maintaining trophoblast invasion and migration. Decidual stromal cells (DSCs), which are predominant at the maternal-fetal interface, have been identified as key regulators of the epithelial-mesenchymal transition (EMT) of trophoblasts, which facilitates their migration and invasion. However, the underlying biological mechanisms remain largely unexplored and constitute the central focus of this study.</p><p><strong>Results: </strong>The inhibition of trophoblast EMT by URSA-DSC-derived exosomes (URSA-DSC-exos) resulted in decreased migration and invasion abilities in vitro. MicroRNA sequencing revealed that miR-92b-3p were the most significantly upregulated microRNA in trophoblasts treated with URSA-DSC-exos. Further functional experiments demonstrated that URSA-DSC-exos inhibited trophoblast migration and invasion by transferring miR-92b-3p. Mechanistically, miR-92b-3p in URSA-DSC-exos suppressed trophoblast migration and invasion by directly downregulating USP28 expression at the post-transcriptional level. Overexpression of USP28 rescue the inhibitory effect of miR-92b-3p mimics on the expression of USP28 and restored the invasion and migration capabilities of HTR-8/SVneo cells. Furthermore, in vivo experiment suggested that URSA-DSC-exos led to increased embryo absorption in mice. Clinically, alterations in USP28 and EMT-related molecule expressions were observed in URSA patients, and a negative correlation was noted between miR-92b-3p and USP28 levels.</p><p><strong>Conclusion: </strong>Our findings has demonstrated that the induction of insufficient migration and invasion of trophoblast by URSA-DSC-exos is due to abnormal ubiquitination degradation, which is mediated by the low expression of USP28, which is suppressed by miR-92b-3p at the post-transcriptional level. Reversing this disorder sheds light on a novel mechanism in DSC regulation of trophoblasts, highlighting their significant role in URSA.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"222"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688897","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}

{"title":"A lethal DENV-2 wild-type mouse model for mutagenesis investigations.","authors":"Zhiran Qin, Xiaoting Xie, Hua Ye, Hao Wu, Zhuoyun Li, Jingshu Li, Xiaoen He, Zuxin Liang, Xuling Liu, Li Zhu, Qinghua Wu, Weiwei Xiao, Kefeng Wu, Chengsong Wan, Bao Zhang, Zhaohui Sun, Jianhai Yu, Chenguang Shen, Linzhong Yu, Wei Zhao","doi":"10.1186/s12915-025-02332-6","DOIUrl":"10.1186/s12915-025-02332-6","url":null,"abstract":"<p><strong>Background: </strong>Effective mouse models for testing antiviral medications should be both cost-effective and require minimal labor. Immunodeficient mouse models, such as AG129, are commonly used in dengue virus (DENV) research; however, their high import and maintenance costs make them relatively expensive. Moreover, the absence of IFN-γ signaling limits the capacity of the AG129 model. To date, wild-type mouse models of DENV infection have only exhibited mild symptoms without lethality, limiting their research applicability. In this study, we developed a lethal C57BL/6 wild-type mouse model infected with DENV-2 365 strain. By blocking the type I interferon receptor before the virus challenge, we allowed the immune response to be restored at a later stage of infection.</p><p><strong>Results: </strong>Following infection, the mice exhibited severe symptoms, including weight loss, high viremia levels, elevated inflammatory cytokines, significant vascular leakage, and pathological changes in the brain, kidney, liver and spleen. The model also displayed severe central nervous symptoms and 100% mortality. Additionally, we used this model to evaluate an adaptable NS2A protein mutation found in both Zika virus and DENV-2.</p><p><strong>Conclusions: </strong>Our study introduces an alternative model design for investigating viral mutations, providing a valuable tool for future research.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"218"},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682065","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}