Pub Date : 2025-12-15DOI: 10.1080/22221751.2025.2601371
Madison E Lee,Clairissa A Hansen,Jill K Thompson,Haiping Hao,Nigel Bourne,Alan D T Barrett
Yellow fever virus (YFV) is the prototypical member of the genus Orthoflavivirus and is responsible for the disease yellow fever. Phylogenetic studies show YFV can be characterized into seven genotypes (East Africa [EA], East and Central Africa [ECA], West Africa I [WAI], West Africa II [WAII], South America I [SAI], South America II [SAII], and Angola [ANG]). We used Next Generation Sequencing to investigate and compare genetic diversity of the seven genotypes of YFV using early isolated strains of known passage history from a variety of collection years. Genetic diversity varied between the seven genotypes, with the ECA genotype being more diverse than EA and WAI genotypes, but not WAII genotype. Genotype-specific amino acids (GSaas) were identified that occurred in all viral proteins but varied by genotype with most being found in the non-structural proteins, which make up the viral replication complex. Interestingly, the fewest GSaas were found in the EA and ECA genotypes despite the ECA genotype having greater genetic diversity than either the EA or WAI genotypes. Overall, based on examination of early strains, we show that genetic diversity and GSaas varied between the seven genotypes of YFV and are not random but likely caused by selection pressure(s) such as different primate and mosquito hosts in different geographic areas. Examination of genetic diversity and GSaas in recent strains will enable genetic diversity to be investigated over time and those involved in outbreaks may enable a better understanding of how outbreaks develop and help identify interventions to their spread.
{"title":"Differences in Genetic Diversity between Early Isolates of Yellow Fever Virus Genotypes.","authors":"Madison E Lee,Clairissa A Hansen,Jill K Thompson,Haiping Hao,Nigel Bourne,Alan D T Barrett","doi":"10.1080/22221751.2025.2601371","DOIUrl":"https://doi.org/10.1080/22221751.2025.2601371","url":null,"abstract":"Yellow fever virus (YFV) is the prototypical member of the genus Orthoflavivirus and is responsible for the disease yellow fever. Phylogenetic studies show YFV can be characterized into seven genotypes (East Africa [EA], East and Central Africa [ECA], West Africa I [WAI], West Africa II [WAII], South America I [SAI], South America II [SAII], and Angola [ANG]). We used Next Generation Sequencing to investigate and compare genetic diversity of the seven genotypes of YFV using early isolated strains of known passage history from a variety of collection years. Genetic diversity varied between the seven genotypes, with the ECA genotype being more diverse than EA and WAI genotypes, but not WAII genotype. Genotype-specific amino acids (GSaas) were identified that occurred in all viral proteins but varied by genotype with most being found in the non-structural proteins, which make up the viral replication complex. Interestingly, the fewest GSaas were found in the EA and ECA genotypes despite the ECA genotype having greater genetic diversity than either the EA or WAI genotypes. Overall, based on examination of early strains, we show that genetic diversity and GSaas varied between the seven genotypes of YFV and are not random but likely caused by selection pressure(s) such as different primate and mosquito hosts in different geographic areas. Examination of genetic diversity and GSaas in recent strains will enable genetic diversity to be investigated over time and those involved in outbreaks may enable a better understanding of how outbreaks develop and help identify interventions to their spread.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"167 1","pages":"2601371"},"PeriodicalIF":13.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1080/22221751.2025.2601372
Philippe Noriel Q Pascua,Anton P Chesnokov,Ha T Nguyen,Chloe Champion,Rongyuan Gao,Juan A De La Cruz,Yunho Jang,Yasuko Hatta,Zhu Guo,Timothy M Uyeki,Han Di,James Stevens,Charles T Davis,Larisa V Gubareva
Since October 2024, 55 human cases of influenza A(H5N1), clade 2.3.4.4b, were reported in the US. Sequencing of 46 viruses identified genotypes B3.13, D1.1, and D1.3. Genomes of viruses were analyzed for mutations associated with reduced antiviral susceptibility. Except for two, viruses from human cases were assessed as susceptible to antivirals and confirmed by in vitro susceptibility testing of representative viruses with M2 blockers, neuraminidase (NA) inhibitors, and the polymerase acidic (PA) inhibitor baloxavir. One D1.1 virus had an M2-S31N substitution, which conferred cross-resistance to M2 blockers. One B3.13 virus had a PA-I38M substitution and displayed 17-fold reduced baloxavir susceptibility in cell culture. In mice, baloxavir, given orally at 5, 15, and 45 mg/kg bid for 5 days starting at 2 hours post-infection, was notably less effective against the PA-I38M virus compared to the closely matched control virus, as shown by survival rate, time-to-death, weight loss, and viral replication in various organs. Replication of the PA-I38M virus was mildly attenuated in mice but not in cell culture. Viruses collected from animals also contained mutations associated with reduced antiviral susceptibility, including M2-S31N, PA-I38 T/M, and NA-H275Y, albeit at low frequency. Regardless of genotype, most mutations were found in NA. Using recombinant NA proteins generated from B3.13 and D1.1 backgrounds, we showed that among mutations that reduced susceptibility of NA inhibitors, only NA-H275Y had no effect on the enzyme's function. Spontaneous emergence of drug-resistant influenza viruses, especially those that maintain replicative fitness, pose persistent threat to human health and must be closely monitored.
{"title":"Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses from humans in the United States, October 2024 to February 2025.","authors":"Philippe Noriel Q Pascua,Anton P Chesnokov,Ha T Nguyen,Chloe Champion,Rongyuan Gao,Juan A De La Cruz,Yunho Jang,Yasuko Hatta,Zhu Guo,Timothy M Uyeki,Han Di,James Stevens,Charles T Davis,Larisa V Gubareva","doi":"10.1080/22221751.2025.2601372","DOIUrl":"https://doi.org/10.1080/22221751.2025.2601372","url":null,"abstract":"Since October 2024, 55 human cases of influenza A(H5N1), clade 2.3.4.4b, were reported in the US. Sequencing of 46 viruses identified genotypes B3.13, D1.1, and D1.3. Genomes of viruses were analyzed for mutations associated with reduced antiviral susceptibility. Except for two, viruses from human cases were assessed as susceptible to antivirals and confirmed by in vitro susceptibility testing of representative viruses with M2 blockers, neuraminidase (NA) inhibitors, and the polymerase acidic (PA) inhibitor baloxavir. One D1.1 virus had an M2-S31N substitution, which conferred cross-resistance to M2 blockers. One B3.13 virus had a PA-I38M substitution and displayed 17-fold reduced baloxavir susceptibility in cell culture. In mice, baloxavir, given orally at 5, 15, and 45 mg/kg bid for 5 days starting at 2 hours post-infection, was notably less effective against the PA-I38M virus compared to the closely matched control virus, as shown by survival rate, time-to-death, weight loss, and viral replication in various organs. Replication of the PA-I38M virus was mildly attenuated in mice but not in cell culture. Viruses collected from animals also contained mutations associated with reduced antiviral susceptibility, including M2-S31N, PA-I38 T/M, and NA-H275Y, albeit at low frequency. Regardless of genotype, most mutations were found in NA. Using recombinant NA proteins generated from B3.13 and D1.1 backgrounds, we showed that among mutations that reduced susceptibility of NA inhibitors, only NA-H275Y had no effect on the enzyme's function. Spontaneous emergence of drug-resistant influenza viruses, especially those that maintain replicative fitness, pose persistent threat to human health and must be closely monitored.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"230 1","pages":"2601372"},"PeriodicalIF":13.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1080/22221751.2025.2602317
Kayla A Holder,Danielle P Ings,Keeley M Hatfield,Kathleen E Fifield,David A Barnes,Keeley A Barnable,Debbie O A Harnum,Michael D Grant
At a population level, evaluation of vaccine efficacy and of immunity in general focuses on measuring humoral immunity, especially antibody-mediated neutralization. However, antibody-dependent cell-mediated cytotoxicity (ADCC) and cellular immunity are key processes for pathogen clearance and often provide broader protection against emerging variants. More information on vaccine and infection-related determinants or markers of cell-mediated cytotoxicity is needed to inform design of standardized, high throughput tests assessing these processes. We previously showed that persons infected with SARS-CoV-2 prior to vaccination (hybrid immunity) had polyfunctional CD8+ T cells and robust ADCC against SARS-CoV-2 spike (S), while persons infected with Omicron after vaccination (breakthrough infection) had weak ADCC. In the current study, we investigated the impact of Omicron breakthrough infection on S-specific cellular immunity, including polyfunctional CD8+ T cell and cytotoxic T lymphocyte (CTL) levels of 28 previously uninfected individuals vaccinated either two or three times against SARS-CoV-2. In the group with three vaccinations, Omicron breakthrough infection significantly increased the frequency of circulating SARS-CoV-2 S-specific T cells, polyfunctional interferon-gamma and interleukin-2-producing SARS-CoV-2 S-specific CD8+ T cells and CTL after in vitro stimulation. Matrix testing with overlapping S peptides indicated recognition of one to two CTL epitopes per individual and revealed two previously unreported epitopes. Circulating S-specific cellular immune response magnitude neither correlated with, nor predicted CTL activity against SARS-CoV-2 S, but polyfunctional S-specific CD8+ T cell frequency seven days after stimulation and antibody reactivity against determinants indicating robust ADCC were both associated with day 10 CTL activity.
{"title":"Predictive Markers of SARS-CoV-2 Spike-specific Cytotoxic T Cell Activity Following Omicron Breakthrough Infection.","authors":"Kayla A Holder,Danielle P Ings,Keeley M Hatfield,Kathleen E Fifield,David A Barnes,Keeley A Barnable,Debbie O A Harnum,Michael D Grant","doi":"10.1080/22221751.2025.2602317","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602317","url":null,"abstract":"At a population level, evaluation of vaccine efficacy and of immunity in general focuses on measuring humoral immunity, especially antibody-mediated neutralization. However, antibody-dependent cell-mediated cytotoxicity (ADCC) and cellular immunity are key processes for pathogen clearance and often provide broader protection against emerging variants. More information on vaccine and infection-related determinants or markers of cell-mediated cytotoxicity is needed to inform design of standardized, high throughput tests assessing these processes. We previously showed that persons infected with SARS-CoV-2 prior to vaccination (hybrid immunity) had polyfunctional CD8+ T cells and robust ADCC against SARS-CoV-2 spike (S), while persons infected with Omicron after vaccination (breakthrough infection) had weak ADCC. In the current study, we investigated the impact of Omicron breakthrough infection on S-specific cellular immunity, including polyfunctional CD8+ T cell and cytotoxic T lymphocyte (CTL) levels of 28 previously uninfected individuals vaccinated either two or three times against SARS-CoV-2. In the group with three vaccinations, Omicron breakthrough infection significantly increased the frequency of circulating SARS-CoV-2 S-specific T cells, polyfunctional interferon-gamma and interleukin-2-producing SARS-CoV-2 S-specific CD8+ T cells and CTL after in vitro stimulation. Matrix testing with overlapping S peptides indicated recognition of one to two CTL epitopes per individual and revealed two previously unreported epitopes. Circulating S-specific cellular immune response magnitude neither correlated with, nor predicted CTL activity against SARS-CoV-2 S, but polyfunctional S-specific CD8+ T cell frequency seven days after stimulation and antibody reactivity against determinants indicating robust ADCC were both associated with day 10 CTL activity.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"30 1","pages":"2602317"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Since July 2025, Foshan has experienced the largest outbreak of Chikungunya fever in China. This single-centre retrospective study included 1,908 laboratory-confirmed cases. Phylogenetic analysis identified the East/Central/South African lineage, closely related to the 2025 La Réunion strain. The included cases were all non-severe, showed no sex bias, but exhibited clear regional clustering. Fever (86.8%), arthralgia (85.4%), and rash (64.1%) were predominant symptoms. Fever and rash were more common in minors, while arthralgia increased with age. Lymphopenia occurred in 65.5% of patients and was more common in elderly patients, who had higher viral loads and longer RNA clearance times. Age, sex and viral load independently influenced clinical manifestations and laboratory characteristics. The findings provide initial descriptive evidence and highlight age-related differences in chikungunya's clinical and virological profiles. Long-term follow-up and larger-scale investigations were necessary to provide evidence for clinical decision-making.
自2025年7月以来，佛山经历了中国最大的基孔肯雅热疫情。这项单中心回顾性研究包括1908例实验室确诊病例。系统发育分析确定了东部/中部/南非谱系，与2025 La r菌株密切相关。纳入病例均为非重症病例，无性别偏倚，但有明显的区域聚集性。发热（86.8%）、关节痛（85.4%）和皮疹（64.1%）是主要症状。发热和皮疹在未成年人中更常见，而关节痛随着年龄的增长而增加。65.5%的患者发生淋巴细胞减少，在老年患者中更为常见，老年患者的病毒载量更高，RNA清除时间更长。年龄、性别和病毒载量独立影响临床表现和实验室特征。这些发现提供了初步的描述性证据，并突出了基孔肯雅热临床和病毒学概况中与年龄相关的差异。为临床决策提供证据需要长期随访和更大规模的调查。
{"title":"An ECSA-lineage Chikungunya Outbreak in Foshan, China: Age-Stratified Clinical and Virological Profiles.","authors":"Zhouhan Wang,Zhifeng Hong,Junfeng Chen,Junyi Wang,Wei Liang,Jingru Wang,Chang Zhang,Zhaoxia Hu,Qifa Shen,Yongqi Zhang,Shunyang Wei,Baisheng Li,Xin Shu,Zaopeng He,Bingliang Lin","doi":"10.1080/22221751.2025.2602308","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602308","url":null,"abstract":"Since July 2025, Foshan has experienced the largest outbreak of Chikungunya fever in China. This single-centre retrospective study included 1,908 laboratory-confirmed cases. Phylogenetic analysis identified the East/Central/South African lineage, closely related to the 2025 La Réunion strain. The included cases were all non-severe, showed no sex bias, but exhibited clear regional clustering. Fever (86.8%), arthralgia (85.4%), and rash (64.1%) were predominant symptoms. Fever and rash were more common in minors, while arthralgia increased with age. Lymphopenia occurred in 65.5% of patients and was more common in elderly patients, who had higher viral loads and longer RNA clearance times. Age, sex and viral load independently influenced clinical manifestations and laboratory characteristics. The findings provide initial descriptive evidence and highlight age-related differences in chikungunya's clinical and virological profiles. Long-term follow-up and larger-scale investigations were necessary to provide evidence for clinical decision-making.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"5 1","pages":"2602308"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1080/22221751.2025.2595753
{"title":"Statement of Retraction: The regulation of cell homeostasis and antiviral innate immunity by autophagy during classical swine fever virus infection.","authors":"","doi":"10.1080/22221751.2025.2595753","DOIUrl":"https://doi.org/10.1080/22221751.2025.2595753","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"1 1","pages":"2595753"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Avian influenza viruses (AIVs) of the H5, H7, and H10 subtypes pose substantial threats to global public health owing to their high pathogenicity, cross-species transmissibility, and potential to spark epidemics. Rapid and accurate detection is essential for outbreak control and zoonotic risk mitigation. Here, we report the development of a multiplex lateral flow immunoassay (LFA) based on core-shell upconversion nanoparticles (UCNPs) conjugated with subtype-specific monoclonal antibodies targeting the haemagglutinin proteins of H5, H7, and H10 AIVs. The assay achieved limits of detection of 0.0313, 0.0156, and 0.0625 ng/mL for recombinant HA proteins and 2-4, 2-4, and 2-3 haemagglutination units for viral titers of H5, H7, and H10, respectively. No cross-reactivity was observed with other AIV subtypes or respiratory pathogens, and intra- and inter-assay variation remained below 6%, demonstrating high specificity and reproducibility. Validation with 135 avian and 125 human clinical samples showed complete concordance with real-time RT-PCR results. Integration with a smartphone-based analytical platform enabled rapid readout, automated quantification, and cloud-based data sharing, providing results within 10 minutes. This intelligent UCNPs-LFA system combines ultra sensitivity, multiplexing, and field-deployable usability, representing a significant advance over conventional methods. By enabling timely and reliable detection of H5, H7, and H10 AIVs in both animal and human samples, this platform offers a practical tool for early warning, surveillance, and control of emerging zoonotic influenza, thereby contributing to global preparedness against avian influenza outbreaks.
{"title":"Smartphone-assisted upconversion nanoparticle assay for rapid multiplex detection of H5, H7, and H10 avian influenza viruses.","authors":"Jun Zhang,Han Wu,Ping Wang,Jiamin Fu,Xinyao Zheng,Fang Wan,Man Hu,Fumin Liu,Linfang Cheng,Hangping Yao,Nanping Wu,Junli Zhu,Haibo Wu","doi":"10.1080/22221751.2025.2602315","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602315","url":null,"abstract":"Avian influenza viruses (AIVs) of the H5, H7, and H10 subtypes pose substantial threats to global public health owing to their high pathogenicity, cross-species transmissibility, and potential to spark epidemics. Rapid and accurate detection is essential for outbreak control and zoonotic risk mitigation. Here, we report the development of a multiplex lateral flow immunoassay (LFA) based on core-shell upconversion nanoparticles (UCNPs) conjugated with subtype-specific monoclonal antibodies targeting the haemagglutinin proteins of H5, H7, and H10 AIVs. The assay achieved limits of detection of 0.0313, 0.0156, and 0.0625 ng/mL for recombinant HA proteins and 2-4, 2-4, and 2-3 haemagglutination units for viral titers of H5, H7, and H10, respectively. No cross-reactivity was observed with other AIV subtypes or respiratory pathogens, and intra- and inter-assay variation remained below 6%, demonstrating high specificity and reproducibility. Validation with 135 avian and 125 human clinical samples showed complete concordance with real-time RT-PCR results. Integration with a smartphone-based analytical platform enabled rapid readout, automated quantification, and cloud-based data sharing, providing results within 10 minutes. This intelligent UCNPs-LFA system combines ultra sensitivity, multiplexing, and field-deployable usability, representing a significant advance over conventional methods. By enabling timely and reliable detection of H5, H7, and H10 AIVs in both animal and human samples, this platform offers a practical tool for early warning, surveillance, and control of emerging zoonotic influenza, thereby contributing to global preparedness against avian influenza outbreaks.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"6 1","pages":"2602315"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The classical swine (CS) H1N1 influenza virus firstly isolated in 1930 is highly homologous to the 1918 Spanish influenza virus. CS H1N1 virus crossed the interspecies barrier to infect humans has become the dominantly prevalent strain in China's pig population, showing a trend of continuous transmission. However, whether subsequent adaptation of CS H1N1 to mammals would increase their pathogenicity toward humans is unknown. To address this, a mouse-adapted (MA) CS H1N1 virus (A/Swine/Guangdong/1/2011[G11-MA]) was generated through serially passaged in mouse lungs, exhibiting increased virulence compared to the wild-type (WT). Further study showed that the G11-MA strain occurred the amino acid mutations in PB2-D740N, PB1-T56I, PA-T97I and HA-K188E, and the combination of PB2-D740N with PA-T97I improved the replication ability in mammalian cells and mice. The G11-MA strain with PB2 and PA (G11/MA PB2PA) group enhanced the viral polymerase activity, with the similar survival rate and weight loss of mice compared to the G11-MA group. Our study demonstrates that the combination of PB2-D740N and PA-T97I plays a key role in the virulence phenotype of CS H1N1 influenza viruses, and provides important information for evaluating the pandemic risk of swine influenza strains.
{"title":"Identification of the Key Amino Acid Mutations in the PB2 and PA Proteins of Classical Swine H1N1 Influenza A Virus in Mammalian Adaptation.","authors":"Xiuhui Wang,Xiaomin Liu,Shuaiyong Wang,Qi Wang,Juan Wang,Manzhu Wang,Yun Yao,Yanjun Zhou,Tongling Shan,Wu Tong,Hao Zheng,Ning Kong,Yifeng Jiang,Changlong Liu,Guangzhi Tong,Hai Yu","doi":"10.1080/22221751.2025.2602310","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602310","url":null,"abstract":"The classical swine (CS) H1N1 influenza virus firstly isolated in 1930 is highly homologous to the 1918 Spanish influenza virus. CS H1N1 virus crossed the interspecies barrier to infect humans has become the dominantly prevalent strain in China's pig population, showing a trend of continuous transmission. However, whether subsequent adaptation of CS H1N1 to mammals would increase their pathogenicity toward humans is unknown. To address this, a mouse-adapted (MA) CS H1N1 virus (A/Swine/Guangdong/1/2011[G11-MA]) was generated through serially passaged in mouse lungs, exhibiting increased virulence compared to the wild-type (WT). Further study showed that the G11-MA strain occurred the amino acid mutations in PB2-D740N, PB1-T56I, PA-T97I and HA-K188E, and the combination of PB2-D740N with PA-T97I improved the replication ability in mammalian cells and mice. The G11-MA strain with PB2 and PA (G11/MA PB2PA) group enhanced the viral polymerase activity, with the similar survival rate and weight loss of mice compared to the G11-MA group. Our study demonstrates that the combination of PB2-D740N and PA-T97I plays a key role in the virulence phenotype of CS H1N1 influenza viruses, and provides important information for evaluating the pandemic risk of swine influenza strains.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"15 1","pages":"2602310"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The monkeypox virus (MPXV), a re-emerging Orthopoxvirus, has triggered unprecedented global outbreaks, with over 130,000 confirmed cases reported by January 2025. Despite its escalating public health threat, the molecular mechanisms governing MPXV-host interactions remain inadequately characterized. In this study, we systematically explored the impact of MPXV Clade IIb infection on the host transcriptome across diverse cell lines, unveiling both conserved and cell-type-specific transcriptomic changes. Our analysis revealed significant disruptions in pathways associated with immune response, cell cycle regulation, metabolism, protein synthesis, and epigenetic modification. Additionally, we evaluated two widely used mRNA sequencing methodologies for MPXV transcriptome profiling, demonstrating that ribosomal RNA depletion offers a more comprehensive representation of viral mRNA compared to poly(A) tail enrichment. Through cross-cell-line comparisons and temporal transcriptomic analysis in A549 cells, we identified stage-specific regulation of MPXV gene expression. Leveraging the temporal host transcriptome profiles, we predicted and validated potential therapeutic targets, demonstrating that inhibitors targeting the mTOR pathway and growth factor receptors effectively inhibit MPXV infection. Collectively, these findings provide critical insights into the intricate interplay between MPXV and its host, offering a foundation for developing antiviral strategies and advancing our understanding of mpox pathogenesis.
{"title":"Cross-Cell Line Transcriptome Profiling Reveals Host-Virus Interactions in Monkeypox Virus Infection.","authors":"Hongyang Yi,Sumei Yang,Jiayu Deng,Xiang Liu,Xiling Zhang,Xiaoxin Xie,Jing Li,Jiahao Wang,Li Wei,Zhenzhong Zheng,Mingxia Zhang,Liang Fang,Hongzhou Lu","doi":"10.1080/22221751.2025.2602311","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602311","url":null,"abstract":"The monkeypox virus (MPXV), a re-emerging Orthopoxvirus, has triggered unprecedented global outbreaks, with over 130,000 confirmed cases reported by January 2025. Despite its escalating public health threat, the molecular mechanisms governing MPXV-host interactions remain inadequately characterized. In this study, we systematically explored the impact of MPXV Clade IIb infection on the host transcriptome across diverse cell lines, unveiling both conserved and cell-type-specific transcriptomic changes. Our analysis revealed significant disruptions in pathways associated with immune response, cell cycle regulation, metabolism, protein synthesis, and epigenetic modification. Additionally, we evaluated two widely used mRNA sequencing methodologies for MPXV transcriptome profiling, demonstrating that ribosomal RNA depletion offers a more comprehensive representation of viral mRNA compared to poly(A) tail enrichment. Through cross-cell-line comparisons and temporal transcriptomic analysis in A549 cells, we identified stage-specific regulation of MPXV gene expression. Leveraging the temporal host transcriptome profiles, we predicted and validated potential therapeutic targets, demonstrating that inhibitors targeting the mTOR pathway and growth factor receptors effectively inhibit MPXV infection. Collectively, these findings provide critical insights into the intricate interplay between MPXV and its host, offering a foundation for developing antiviral strategies and advancing our understanding of mpox pathogenesis.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"44 1","pages":"2602311"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1080/22221751.2025.2601370
Héctor Carmona-Salido,Rubén Salvador-Clavell,Claudia Jäckel,Isabelle Schulze,Karla J F Satchell,Jens Andre Hammerl,Carmen Amaro
Climate-driven changes are reshaping the ecology of Vibrio vulnificus in European waters. Here, we present a retrospective genomic and phenotypic analysis of pre-2018 isolates belonging to lineage 4 (L4), a phylogenetic group historically confined to the Mediterranean Sea and now detected in northern Europe. Using a lineage-specific multiplex PCR combined with whole-genome sequencing, we identified 49 clinical and environmental L4 isolates from German coastal waters. Comparative genomics revealed extensive genetic plasticity in L4, indicative of frequent recombination and horizontal gene transfer, including three MARTX toxin architectures, fourteen distinct capsular genotypes, two type VI secretion systems, and multiple prophages. Notably, nearly half of the L4 isolates encoded a previously undescribed MARTX variant (type H), apparently derived from recombination within a type C toxin and containing a novel calmodulin-dependent NADase (CdN) domain with potential functional implications for virulence. One strain also harboured the plasmid-borne genes ftbp and fpcrp, which confer resistance to fish innate immunity and the ability to cause sepsis, thereby extending the distribution of the piscis pathovar to all five V. vulnificus lineages. Functional assays showed that most L4 strains withstood the bactericidal activity of iron-overloaded human serum, consistent with a capacity to cause sepsis in susceptible individuals. Collectively, these findings redefine V. vulnificus as a multi-host climate-responsive marine pathogen and establish L4 as a newly adapted European lineage whose northward expansion exemplifies how genomic diversification and ocean warming jointly drive the evolution of high-risk marine pathogens within a One Health framework.
{"title":"Emergence, climate-driven expansion, and diversification of a European Vibrio vulnificus lineage (L4) with multi-host pathogenic potential.","authors":"Héctor Carmona-Salido,Rubén Salvador-Clavell,Claudia Jäckel,Isabelle Schulze,Karla J F Satchell,Jens Andre Hammerl,Carmen Amaro","doi":"10.1080/22221751.2025.2601370","DOIUrl":"https://doi.org/10.1080/22221751.2025.2601370","url":null,"abstract":"Climate-driven changes are reshaping the ecology of Vibrio vulnificus in European waters. Here, we present a retrospective genomic and phenotypic analysis of pre-2018 isolates belonging to lineage 4 (L4), a phylogenetic group historically confined to the Mediterranean Sea and now detected in northern Europe. Using a lineage-specific multiplex PCR combined with whole-genome sequencing, we identified 49 clinical and environmental L4 isolates from German coastal waters. Comparative genomics revealed extensive genetic plasticity in L4, indicative of frequent recombination and horizontal gene transfer, including three MARTX toxin architectures, fourteen distinct capsular genotypes, two type VI secretion systems, and multiple prophages. Notably, nearly half of the L4 isolates encoded a previously undescribed MARTX variant (type H), apparently derived from recombination within a type C toxin and containing a novel calmodulin-dependent NADase (CdN) domain with potential functional implications for virulence. One strain also harboured the plasmid-borne genes ftbp and fpcrp, which confer resistance to fish innate immunity and the ability to cause sepsis, thereby extending the distribution of the piscis pathovar to all five V. vulnificus lineages. Functional assays showed that most L4 strains withstood the bactericidal activity of iron-overloaded human serum, consistent with a capacity to cause sepsis in susceptible individuals. Collectively, these findings redefine V. vulnificus as a multi-host climate-responsive marine pathogen and establish L4 as a newly adapted European lineage whose northward expansion exemplifies how genomic diversification and ocean warming jointly drive the evolution of high-risk marine pathogens within a One Health framework.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"29 1","pages":"2601370"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A multicenter cross-sectional study was conducted across six Chinese hospitals between September 2023 and April 2024 to investigate the prevalence, molecular epidemiology, antimicrobial resistance (AMR) and genetic relatedness of C. difficile in pediatric populations. Among 1,442 stool samples collected, 242 C. difficile isolates were recovered (16.8%), including 188 from asymptomatic carriers (13.0%) and 11 from confirmed C. difficile infection (CDI) cases (0.98%). The highest rate of asymptomatic carriage was observed in children aged 1-2 years (29.3%). Multilocus sequence typing (MLST) identified ST3 as the predominant sequence type (30.6%), followed by ST42, ST54, ST2, ST102, and ST110. Core genome phylogenetic analysis revealed nine distinct genetic lineages, with lineage VI being the most prevalent among CDI cases. High resistance to clindamycin (64.5%) was observed, primarily mediated by ermB, while all isolates remained susceptible to metronidazole and vancomycin. Moxifloxacin resistance (10.7%) was associated with gyrA T82I mutations, particularly in toxigenic ST3 strains. Transposon analysis indicated ST-specific carriage of AMR genes, with Tn6218(ermB) prevalent in nontoxigenic ST3 isolates and Tn5801 (tet(M)) predominant in ST54. Genomic relatedness (≤2 SNPs) was detected in 12.0% of asymptomatic carriers, with most links associated with hospital-wide contact, suggesting possible transmission events. This study highlights the importance of asymptomatic colonized children as a reservoir for C. difficile, maintaining resistant lineages and disseminating AMR, thereby underscoring the need for enhanced surveillance and targeted antimicrobial stewardship in Chinese healthcare settings.
{"title":"The prevalence and molecular epidemiology of Clostridioides difficile in hospital-based pediatric populations in China.","authors":"Yu Zeng,Yining Shen,Fangfang Fan,Yiyue Liu,Tongxuan Su,Qianli Zhao,Wei Chen,Cen Jiang,Qi Ni,Ru Fan,Manyuan Li,Danfeng Dong,Yibing Peng","doi":"10.1080/22221751.2025.2602319","DOIUrl":"https://doi.org/10.1080/22221751.2025.2602319","url":null,"abstract":"A multicenter cross-sectional study was conducted across six Chinese hospitals between September 2023 and April 2024 to investigate the prevalence, molecular epidemiology, antimicrobial resistance (AMR) and genetic relatedness of C. difficile in pediatric populations. Among 1,442 stool samples collected, 242 C. difficile isolates were recovered (16.8%), including 188 from asymptomatic carriers (13.0%) and 11 from confirmed C. difficile infection (CDI) cases (0.98%). The highest rate of asymptomatic carriage was observed in children aged 1-2 years (29.3%). Multilocus sequence typing (MLST) identified ST3 as the predominant sequence type (30.6%), followed by ST42, ST54, ST2, ST102, and ST110. Core genome phylogenetic analysis revealed nine distinct genetic lineages, with lineage VI being the most prevalent among CDI cases. High resistance to clindamycin (64.5%) was observed, primarily mediated by ermB, while all isolates remained susceptible to metronidazole and vancomycin. Moxifloxacin resistance (10.7%) was associated with gyrA T82I mutations, particularly in toxigenic ST3 strains. Transposon analysis indicated ST-specific carriage of AMR genes, with Tn6218(ermB) prevalent in nontoxigenic ST3 isolates and Tn5801 (tet(M)) predominant in ST54. Genomic relatedness (≤2 SNPs) was detected in 12.0% of asymptomatic carriers, with most links associated with hospital-wide contact, suggesting possible transmission events. This study highlights the importance of asymptomatic colonized children as a reservoir for C. difficile, maintaining resistant lineages and disseminating AMR, thereby underscoring the need for enhanced surveillance and targeted antimicrobial stewardship in Chinese healthcare settings.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"55 1","pages":"2602319"},"PeriodicalIF":13.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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