Emerging Microbes & Infections最新文献

{"title":"Rapid differentiation of VLA1553 and wild-type ECSA chikungunya strains in the context of an IXCHIQ vaccination campaign.","authors":"Laura Pezzi, Etienne Frumence, Konrad Wesselmann, Gregory Mollé, Lucie Falgous, Nazli Ayhan, Raphaelle Klitting, Guillaume André Durand, Gilda Grard, Emilie Mosnier, Patrick Gérardin, Antoine Nougairède, Remi Charrel, Marie-Christine Jaffar-Bandjee, Xavier de Lamballerie","doi":"10.1080/22221751.2026.2674363","DOIUrl":"10.1080/22221751.2026.2674363","url":null,"abstract":"<p><p>In 2024-2025, Réunion Island experienced a large outbreak driven by East-Central-South African (ECSA)-2 lineage of chikungunya virus (CHIKV), leading to the implementation of a vaccination campaign using live-attenuated IXCHIQ (VLA1553). Currently, distinguishing vaccine-derived viremia from wild-type infection relies on genomic sequencing, which is resource-intensive and not routinely available in many diagnostic laboratories. To address this gap, we developed a duplex real-time RT-qPCR assay specifically designed to differentiate VLA1553 from wild-type ECSA strains circulating in La Réunion. The assay targets the non-structural protein 3 hypervariable region, including the 61-amino-acid deletion characteristic of the VLA1553 backbone. Analytical performance was assessed using a panel of CHIKV isolates representing different lineages and a VLA1553-like strain generated using an Infectious Subgenomic Amplicon system. Clinical performance was evaluated using samples from recently vaccinated individuals and patients infected with ECSA-2 strains, and compared with two RT-qPCR assays routinely used by the French National Reference Centers for arboviruses. The duplex assay proved to be specific, detecting wild-type ECSA strains exclusively in the FAM channel and the vaccine strain exclusively in the HEX channel, with no cross-reactivity. It demonstrated high sensitivity, with LOD95 values of 0.9 and 1.1 copies/µL for the vaccine-specific and wild-type-specific targets, respectively. All clinical samples were correctly classified, including one vaccinated individual simultaneously infected with a circulating wild-type strain, as confirmed by sequencing. This duplex assay provides a rapid and reliable method to distinguish vaccine-derived from naturally-acquired CHIKV viremia, supporting more accurate clinical and epidemiological investigations in settings where vaccination and viral circulation overlap.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2674363"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced immunogenicity and dose-sparing efficacy of self-amplifying RNA vaccines against seasonal influenza across subtypes.","authors":"Mengting Huang, Yun Quan, Ruyi Chen, Hao Gu, Wenjun Song, Feng Zhu, Simin Feng, Jinzhong Lin, Jing Lu, Xuechun Li, Wansheng Li, Qianyu Pan, Hongli Li, Lei Sun, Tao Jiang, Bihui Zhang, Xinqian Yin, Dandan Wei, Changrong Yang, Donglan Liu, Zhongfang Wang, Weixin Jia, Jincun Zhao, Jieshi Yu, Xiaobo Li, Xuedong Yu, Xiaojing Yue, Chufang Li, Fan Bu, Zhichao Miao, Qiong Zhang","doi":"10.1080/22221751.2026.2668752","DOIUrl":"10.1080/22221751.2026.2668752","url":null,"abstract":"<p><p>Recent clinical data on seasonal influenza mRNA vaccines have demonstrated suboptimal efficacy against the influenza B virus (IBV). We employed sequence optimization strategies that successfully enhanced the antigen expression of hemagglutinin (HA) and developed mRNA vaccine candidates targeting the WHO-recommended strains. When administered at a low dose (0.1 μg), both mono-and trivalent influenza A mRNA vaccines induced robust humoral immunity and conferred complete protection against homologous viral challenge in murine models, outperforming the quadrivalent inactivated vaccine (QIV, 2 μg). In contrast, IBV mRNA vaccines at an equivalent dose failed to elicit detectable antibodies and offered no protection, consistent with prior evidence of suboptimal immunogenicity in human trials. These findings highlight strain-specific immunogenicity constraints inherent to conventional mRNA platforms. To overcome these limitations, we systematically compared three distinct RNA vaccine modalities: (1) nucleoside-modified mRNA, (2) self-amplifying RNA (saRNA), and (3) circular RNA (circRNA). Notably, a single 0.1 µg dose of the trivalent saRNA vaccine elicited robust humoral immunity and provided complete protection against IBV challenge, whereas mRNA vaccination achieved only 14% survival. Importantly, long-term antibody monitoring over 20 weeks showed that saRNA at the low 0.1 μg dose maintained high antibody levels, with a markedly more durable response to IBV antigens than those of other platforms. Moreover, the trivalent mRNA vaccine exhibited a favourable safety profile, with no obvious abnormal body weight changes or serum biochemical abnormalities observed after immunization. Our findings advocate for strain-adaptive platform selection: conventional mRNA for generating rapid, high-magnitude responses against influenza A and next-generation saRNA vaccines for enhanced dose efficiency, particularly against IBV.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2668752"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond <i>difficile</i>: three novel toxin B-producing <i>Clostridioides</i> species from human patients with diarrhea.","authors":"Daniela Aguilar, Thomas Riedel, Sandra Maaß, Anke Trautwein-Schult, Meina Neumann-Schaal, Sarah Kirstein, Isabel Schober, Boyke Bunk, Luis Acuña-Amador, Diana López-Ureña, Carlos Quesada-Gómez, Dörte Becher, Jörg Overmann, César Rodríguez","doi":"10.1080/22221751.2026.2671473","DOIUrl":"10.1080/22221751.2026.2671473","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> infection (CDI), primarily mediated by toxin B (TcdB), is a leading cause of healthcare-associated and community-acquired diarrhea worldwide. Although this genus exhibits substantial genomic diversity, functional studies have focused mainly on a limited set of isolates, leaving other genomospecies understudied in this regard. Here, we characterized five isolates derived from five distinct patients with suspected CDI cases that tested negative for the <i>tcdC</i> PaLoc marker. Integrated genomic, proteomic, and phenotypic analyses confirm that these strains constitute three novel toxin-producing species and their distinct carbon utilization profiles, exoproteomes, and spore protein repertoires suggest niche specialization within the human gut ecosystem. These species harbour monotoxin PaLoc architectures encoding TcdB7 or TcdB11, located on either chromosomal or extrachromosomal elements, which frequently co-occur with binary toxin loci. Functional assays confirmed secretion of active TcdB, cytotoxicity in mammalian cells, and moderate enterotoxicity in a murine ileal loop model, although virulence was attenuated relative to <i>C. difficile</i> R20291 from Clade 2. Collectively, these findings expand the taxonomy of toxigenic <i>Clostridioides</i>, highlight the dynamic evolution of TcdB-mediated pathogenicity, and emphasize the importance of refining diagnostic workflows and surveillance strategies to address emerging diarrheal diseases. The three novel species were designated <i>as Clostridioides cryptodifficilis</i> sp. nov., <i>Clostridioides divergens</i> sp. nov., and <i>Clostridioides subdifficilis</i> sp. nov.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2671473"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergent evolution of the N156K mutation in A(H1N1)pdm09 hemagglutinin contributes to antigenic drift and cluster transition.","authors":"Yabin Tian, Deyun Jiang, Wentai Ma, Jianhui Nie, Qianqian Li, Chenyan Zhao, Sihong Xu, Weijin Huang, Youchun Wang","doi":"10.1080/22221751.2026.2687185","DOIUrl":"10.1080/22221751.2026.2687185","url":null,"abstract":"<p><p>The continuous antigenic evolution of influenza A(H1N1)pdm09 poses a persistent challenge to vaccine efficacy. While recent viral lineages have diverged significantly from ancestral strains, the precise molecular determinants driving the latest antigenic cluster transitions remain incompletely characterized. Here, using the broadly neutralizing monoclonal antibody 32D6 as a molecular probe, we identified a critical escape mechanism of antibody evasion in recent A(H1N1)pdm09 isolates. Through pseudovirus neutralization assays and LASSO regression analysis, we identified residue 156 in the Sa antigenic site as the key determinant of escape. Furthermore, molecular dynamics (MD) simulations and MM-GBSA calculations indicated that the N156 K mutation reduces the binding free energy at the antibody-antigen interface due to steric hindrance and electrostatic repulsion. Notably, while the N156 K mutations caused a significant reduction in pseudovirus infectivity within the earlier GD19 genetic backbone, it was fully accommodated in recent lineages. Phylogenetic analysis revealed the rapid, convergent fixation of N156 K across global isolates. These findings provide insights into the mechanism of the recent GD19-to-VI19 antigenic transition and highlight the hypothesized role of compensatory mutations in sustaining viral fitness during antigenic evolution.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2687185"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Rv1471-expressing chimpanzee adenovirus vaccine confers protection against tuberculosis by inducing alveolar macrophage trained immunity and polyfunctional T-cell responses.","authors":"Huiling Wang, Ying Zhang, Jianhui Li, Juan Wu, Shaoqiong Huang, Shiqi Xie, Xuejiao Huang, Jing Wang, Xiao-Yong Fan, Zhidong Hu","doi":"10.1080/22221751.2026.2637292","DOIUrl":"10.1080/22221751.2026.2637292","url":null,"abstract":"<p><p>The limited protection afforded by Bacille Calmette-Guérin (BCG) against pulmonary tuberculosis (TB) underscores the critical need for novel vaccine strategies. Alveolar macrophages (AMs), as the primary sentinel cells encountering inhaled <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), play a decisive role in early infection outcomes, yet their potential as a direct vaccine target remains largely untapped. Here, we developed a chimpanzee adenovirus vaccine expressing the <i>Mtb</i> antigen Rv1471 (rAd-Rv1471), which we previously identified for its unique capacity to induce innate immune memory. In murine models, intranasal rAd-Rv1471 administration reprogrammed AMs into a trained state, characterized by enhanced production of pro-inflammatory cytokines, elevated surface expression of MHC II and CD86, and improved cell-intrinsic control of intracellular mycobacterial growth. Transcriptomic analysis revealed upregulation of key immunometabolic pathways, including Akt/mTOR/HIF-1α signalling and glycolysis. Concurrently, intranasal rAd-Rv1471 administration induced potent antigen-specific, polyfunctional T cells in the lung. This dual engagement of innate and adaptive immunity conferred significant protection against aerosol <i>Mtb</i> challenge. Furthermore, rAd-Rv1471 acted as an effective heterologous booster, enhancing protection in BCG-primed mice. Our findings establish rAd-Rv1471 as a synergistic mucosal vaccine candidate that concurrently induces trained immunity in AMs and polyfunctional T-cell responses, highlighting a promising dual-targeting strategy for next-generation TB vaccines.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2637292"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Chikungunya virus infection and pregnancy outcomes: a global systematic review and meta-analysis of vertical transmission dynamics and associated morbidity.","authors":"Yan Guo, Yujie Xiang, Mengyuan Zheng, Zhouling Pan, Yanxian Jiang, Wei Chang, Gaowen Liu, Yonghan Luo, A-Mei Zhang, Li Liu, Yuanyuan Zhang, Caifen Zhu, Jie Zhang, Yue Feng, Xueshan Xia","doi":"10.1080/22221751.2026.2651466","DOIUrl":"10.1080/22221751.2026.2651466","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) infection during pregnancy presents a major threat to maternal-fetal health, yet a comprehensive global assessment of vertical transmission risks and perinatal outcomes remains scarce. To provide a comprehensive evidence synthesis, we conducted a systematic review and meta-analysis, prospectively registered in PROSPERO (CRD420251164423). We screened studies published up to October 20, 2025, and included 57 observational studies for qualitative synthesis, with 27 studies pooled in meta-analyses. The pooled vertical transmission rate was 18.1%, revealing a pronounced gestational-age gradient: rates were low in the first (3.9%) and second (1.2%) trimesters but surged dramatically during the third trimester (36.5%) and the intrapartum period (49.1%). Adverse pregnancy outcomes occurred in 11.3% of infected women, with abnormal fetal heart rate (44.9%) and stillbirth (22.0%) being the most frequent. Among neonates, 36.5% experienced adverse outcomes, commonly including feeding difficulties (79.4%), fever (68.9%), and thrombocytopenia (57.2%); neonatal mortality reached 6.9%. Crucially, meta-analysis of comparative studies demonstrated that maternal CHIKV infection was associated with a more than two-fold higher risk of adverse perinatal outcomes (OR = 2.28), with particularly robust associations identified for abnormal fetal heart rate (OR = 5.07) and delayed neurodevelopment (OR = 11.98). This study underscores that maternal CHIKV infection, especially during late gestation, substantially elevates the risks of vertical transmission and severe perinatal complications. Consequently, our findings strongly advocate for the implementation of enhanced prenatal surveillance and systematic postnatal assessment protocols in CHIKV-endemic regions to mitigate adverse outcomes and guide public health interventions.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2651466"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-emerging Marburg virus disease in Africa: spillover ecology, geographic expansion, and surveillance vulnerabilities.","authors":"Markos Tibbo, Robert Barigye, Gobena Ameni","doi":"10.1080/22221751.2026.2728744","DOIUrl":"10.1080/22221751.2026.2728744","url":null,"abstract":"<p><p>Marburg virus disease (MVD) is re-emerging across Africa as a high-consequence zoonosis shaped by expanding ecological suitability, repeated spillover, and uneven surveillance capacity. This review synthesizes current evidence on the ecological, epidemiological, and operational determinants of contemporary Marburg virus (MARV) emergence. We conceptualize MVD as an ecological-emergence system produced by interactions among reservoir-host biology, environmental change, human exposure, health-system readiness, and mobility, rather than as a series of isolated outbreaks. Recent detections in multiple African regions indicate wider enzootic circulation than previously recognized and support repeated, reservoir-associated introductions from distributed ecological foci. Spillover risk is heightened where mining, land-use change, agricultural encroachment, settlement growth, climate-sensitive habitat disruption, and population movement increase contact with Egyptian rousette bats (<i>Rousettus aegyptiacus</i>) and contaminated roost environments. Following primary spillover, diagnostic delays, fragmented surveillance, limited laboratory decentralization, healthcare-associated transmission, and mobility-linked exposure can enable outbreak amplification and delayed recognition. Serological findings further suggest possible \"shadow epidemiology,\" with unrecognized or mild MARV infections occurring outside confirmed outbreak chains. Critical preparedness gaps persist in ecological risk mapping, longitudinal reservoir surveillance, decentralized molecular diagnostics, genomic sequencing, data integration, and cross-border early warning. Future preparedness should move beyond reactive containment toward integrated One Health approach combining predictive ecological surveillance, rapid community-level detection, real-time genomics, infection prevention, risk communication, and regional coordination to identify spillover early and prevent human transmission.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2728744"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and application of a multiplex qPCR panel for multi-host surveillance of tick-Borne pathogens.","authors":"Jing Li, Zhen Wang, Jing Li, Xinting Meng, Jiaxun Zhang, Wenjin Mao, Yan Hai, Ying Zhang, Xiangxiang Sun, Jin Che, Xiaofang Ma, Biao Duan, Aiping Qin, Jie Liu","doi":"10.1080/22221751.2026.2731498","DOIUrl":"10.1080/22221751.2026.2731498","url":null,"abstract":"<p><p>Tick-borne diseases pose significant public health threats. Non-specific symptoms and co-infections present diagnostic challenges for conventional methods. To address this, we developed the tick-borne pathogen (TBP) Panel, utilizing eight separate multiplex qPCR assays to simultaneously detect 25 TBPs (7 bacteria, 14 viruses, 4 parasites). Optimal Quantification Cycle (Cq) cut-offs were established using nested/semi-nested PCR amplicon sequencing, and digital PCR as reference standards. The Panel was then deployed for screening 2,333 ticks, 59 rodents, and 553 febrile patients. The Panel demonstrated robust analytical performance, achieving limits of detection (LOD_99%) being 3.5-131 copies/reaction of plasmid, 10²-10³ copies/mL of blood and 10³-10⁴ copies/tick pool. This study established a tiered determination framework (Cq ≤ 36.6 as positive; Cq 36.6-39.6 requiring dual-replicate confirmation), yielding an overall AUC of 0.979, with 96.5% sensitivity and 96.5% specificity. Screening revealed a diverse pathogen landscape, identifying a total of 14 pathogens in 16.9% of the ticks (395/2,333), revealing a diverse geographical distribution. Five pathogens were identified in 7.9% of AFI patients (25/317), including Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and <i>Ehrlichia</i> spp., which were found circulating in local ticks. In the FUO cohort, a single case of <i>Rickettsia</i> spp. was identified. Rodent surveillance identified four pathogens, predominantly <i>Bartonella</i> spp. (67.8%). In conclusion , the rigorously validated TBP Panel enables rapid etiological identification of undifferentiated febrile illnesses, serving as a high-throughput tool that bridges large-scale surveillance with clinical diagnostics to close critical gaps in tick-borne disease management.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2731498"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular pathogenesis, global epidemiological trends, and treatment strategies for pteropine orthoreoviruses: a narrative review.","authors":"Francesco Branda, Giancarlo Ceccarelli, Ranjan K Mohapatra, Mohamed Mustaf Ahmed, Uthman Okikiola Adebayo, Dong Keon Yon, Antonello Maruotti, Fabio Scarpa, Massimo Ciccozzi","doi":"10.1080/22221751.2026.2732705","DOIUrl":"10.1080/22221751.2026.2732705","url":null,"abstract":"<p><p>Pteropine orthoreoviruses are emerging bat-borne zoonotic viruses of the genus <i>Orthoreovirus</i> (family <i>Reoviridae</i>), increasingly recognized as causes of acute respiratory disease in humans. Originally grouped with the largely non-pathogenic mammalian orthoreoviruses, they have challenged that view through their association with severe influenza-like illness, evidence of human-to-human transmission, and a broad geographic range across the Old World. Maintained primarily in fruit bats of the family <i>Pteropodidae</i>, they are now linked to neurological as well as respiratory disease. This narrative review synthesizes current knowledge of their molecular pathogenesis, zoonotic ecology, and global epidemiology, integrating recent advances in phylogeography, reassortment-driven evolution, spillover dynamics, and translational biomedical applications within a unified One Health framework. Genomic diversity, reassortment potential, and the unique fusion-associated small transmembrane proteins together underpin viral adaptability and pathogenicity. Major gaps nonetheless remain in transmission dynamics, host adaptation, shedding ecology, and pandemic potential. Future priorities should include integrated genomic surveillance, improved diagnostic strategies, validated experimental models, and interdisciplinary One Health approaches to strengthen outbreak preparedness and prevention.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2732705"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triacylglycerol metabolism is a novel target to combat West Nile virus infection.","authors":"Flavia Caridi, Patricia Mingo-Casas, Ana Esteban, Teresa Poderoso, Nereida Jiménez de Oya, Eva Calvo-Pinilla, Bo Zhang, Eva-María Priego, María-Jesús Pérez-Pérez, Ana-Belén Blázquez, Miguel A Martín-Acebes","doi":"10.1080/22221751.2026.2728216","DOIUrl":"10.1080/22221751.2026.2728216","url":null,"abstract":"<p><p>West Nile virus (WNV) is a zoonotic <i>Orthoflavivirus</i> transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection-driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2728216"},"PeriodicalIF":7.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}