AbstractMonkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a Congo basin country, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to under sampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view on the genomic diversity of MPXV in the Central African region.
{"title":"Genomic Diversity of Clade Ia Monkeypox Virus in the Central African Republic, 2019-2024.","authors":"Alexander Tendu,Lingjing Mao,Stéphane Descorps-Declère,Benjamin Selekon,Ella Farra,Camille Besombes,Sandra Garba-Ouangole,Huguette Dorine Simo,Délia Doreen Djuicy,Raphäel Mbaïlao,Jean Méthode Moyen,Ernest Kalthan,Pierre Somse,Thomas D'aquin Koyazegbet,Richard Njouom,Sebastian Duchene,Arnaud Fontanet,Gary Wong,Emmanuel Nakouné,Antoine Gessain,Nicolas Berthet","doi":"10.1080/22221751.2026.2645863","DOIUrl":"https://doi.org/10.1080/22221751.2026.2645863","url":null,"abstract":"AbstractMonkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a Congo basin country, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to under sampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view on the genomic diversity of MPXV in the Central African region.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2645863"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447064","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}
African Swine Fever Virus (ASFV) continues to mutate uncontrollably, with outbreaks caused by genotype II strains inflicting substantial economic losses on the global swine industry. Currently, a more virulent recombinant strain, combining genotype I and II, is spreading across China, Russia and Vietnam, exacerbating the severity of the epidemic. The development of safe and effective ASFV vaccines is therefore urgent. We constructed two gene-deleted strains - SY18ΔD250R (genotype II) and JX23-02ΔD250R (genotype I/II recombinant) - by knocking out the D250R gene from virulent field strains. Both strains were significantly attenuated and induced robust humoral and cellular immune responses in vaccinated pigs, with no clinical signs or mortality observed post-vaccination. Pigs immunized with SY18ΔD250R showed 80% protection (4/5 survived) against homologous SY18 challenge. Pig #60, which succumbed to infection, exhibited persistently negative humoral responses (p54 antibody) and the lowest cell-mediated immunity (IFN-γ response) within the group. The vaccinated pigs demonstrated cross-protection against an attenuated genotype II strain but failed to resist heterologous challenge with genotype I/II ASFV strain, even after booster immunization. In contrast, JX23-02ΔD250R-immunized pigs achieved 100% survival against both the parental I/II recombinant strain and virulent genotype II strains, with rapid viral clearance and low tissue viral loads. Notably, both SY18ΔD250R and JX23-02ΔD250R exhibited low or undetectable shedding, viremia, and viral loads-offering a significant safety advantage. Thus, JX23-02ΔD250R represents a promising vaccine candidate with potential for application against circulating ASFV strains.
{"title":"Hybrid genotype I and II ASFV D250R deletions confer protection against parental and genotype II strains and elicit potent immune response.","authors":"Xiaoying Jia,Nan Li,Xuefei Sun,Junnan Ke,Min Zheng,Fengjie Wang,Huixian Yue,Zhuo Hao,Yiqian Jiang,Qixuan Li,Teng Chen,Yu Qi,Ying Wang,Shoufeng Zhang,Shuchao Wang,Rongliang Hu,Faming Miao,Yanyan Zhang","doi":"10.1080/22221751.2026.2640697","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640697","url":null,"abstract":"African Swine Fever Virus (ASFV) continues to mutate uncontrollably, with outbreaks caused by genotype II strains inflicting substantial economic losses on the global swine industry. Currently, a more virulent recombinant strain, combining genotype I and II, is spreading across China, Russia and Vietnam, exacerbating the severity of the epidemic. The development of safe and effective ASFV vaccines is therefore urgent. We constructed two gene-deleted strains - SY18ΔD250R (genotype II) and JX23-02ΔD250R (genotype I/II recombinant) - by knocking out the D250R gene from virulent field strains. Both strains were significantly attenuated and induced robust humoral and cellular immune responses in vaccinated pigs, with no clinical signs or mortality observed post-vaccination. Pigs immunized with SY18ΔD250R showed 80% protection (4/5 survived) against homologous SY18 challenge. Pig #60, which succumbed to infection, exhibited persistently negative humoral responses (p54 antibody) and the lowest cell-mediated immunity (IFN-γ response) within the group. The vaccinated pigs demonstrated cross-protection against an attenuated genotype II strain but failed to resist heterologous challenge with genotype I/II ASFV strain, even after booster immunization. In contrast, JX23-02ΔD250R-immunized pigs achieved 100% survival against both the parental I/II recombinant strain and virulent genotype II strains, with rapid viral clearance and low tissue viral loads. Notably, both SY18ΔD250R and JX23-02ΔD250R exhibited low or undetectable shedding, viremia, and viral loads-offering a significant safety advantage. Thus, JX23-02ΔD250R represents a promising vaccine candidate with potential for application against circulating ASFV strains.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"8 1","pages":"2640697"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439294","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}
African swine fever (ASF) is an acute transmissible disease caused by the African swine fever virus (ASFV), which has evolved multiple mechanisms to circumvent the host immune response. This research reveals that ASFV pI73R (I73R protein) downregulates cGAS-STING-mediated interferon beta (IFN-β) activation. ASFV pI73R binds to TBK1 and IRF3 mRNAs, promoting their nuclear retention and attenuating IFN-β production. Furthermore, silencing I73R enhances IFN-β mRNA levels and increases TBK1 and IRF3 protein levels in primary porcine alveolar macrophages (PAMs) exposed to ASFV. Unlike other reported mechanisms of inhibition of IFN-β by other ASFV proteins, pI73R inhibits IFN-β through its RNA binding function. Using structure-based virtual screening, we identified a small-molecule compound, STL527159, which disrupts the pI73R-RNA interaction, thereby restoring nuclear export and translation of the target TBK1 and IRF3 mRNAs. This compound markedly reduced ASFV infection in vitro. These findings provide new perspectives on the immune evasion strategies used by ASFV and offer a novel theoretical foundation for the development of antiviral drugs and novel vaccine candidates against ASFV.
{"title":"African swine fever virus pI73R hijacks host mRNA to suppress interferon beta and reveals a druggable target for antiviral intervention.","authors":"Xia Huang,Xilong Kang,Yongxin Hu,Shunzi Han,Jiarong Yu,Chuang Meng,Dan Gu,Hongqin Song,Zhiliang Wang,Xinan Jiao,Zhiming Pan","doi":"10.1080/22221751.2026.2640703","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640703","url":null,"abstract":"African swine fever (ASF) is an acute transmissible disease caused by the African swine fever virus (ASFV), which has evolved multiple mechanisms to circumvent the host immune response. This research reveals that ASFV pI73R (I73R protein) downregulates cGAS-STING-mediated interferon beta (IFN-β) activation. ASFV pI73R binds to TBK1 and IRF3 mRNAs, promoting their nuclear retention and attenuating IFN-β production. Furthermore, silencing I73R enhances IFN-β mRNA levels and increases TBK1 and IRF3 protein levels in primary porcine alveolar macrophages (PAMs) exposed to ASFV. Unlike other reported mechanisms of inhibition of IFN-β by other ASFV proteins, pI73R inhibits IFN-β through its RNA binding function. Using structure-based virtual screening, we identified a small-molecule compound, STL527159, which disrupts the pI73R-RNA interaction, thereby restoring nuclear export and translation of the target TBK1 and IRF3 mRNAs. This compound markedly reduced ASFV infection in vitro. These findings provide new perspectives on the immune evasion strategies used by ASFV and offer a novel theoretical foundation for the development of antiviral drugs and novel vaccine candidates against ASFV.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"109 1","pages":"2640703"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439295","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 : 2026-03-10DOI: 10.1080/22221751.2026.2640282
Meng Li,Long Cai,Qian Gao
Asymptomatic tuberculosis (TB) poses a major challenge to global TB control. Quantifying its contribution to transmission remains a critical question. Although modelling studies have attempted to address this issue, empirical evidence from real-world settings is scarce. In this study, we estimated the contribution of asymptomatic TB to transmission in China using genomic epidemiology data from five population-based studies, encompassing 6,387 TB patients and 1,626 genomic-clustered patients. Transmission were classified as originating from either asymptomatic or symptomatic TB by comparing reported symptom onset dates with phybreak-inferred transmission timings. Across the study regions, 25.0%-51.3% of transmission was attributed to asymptomatic TB, indicating its substantial role in sustaining transmission. However, accurate estimation is hindered by the subjectivity of symptom reporting and reliance on passive case-finding. While this study likely underestimates the true contribution, it establishes a genomic epidemiology-based framework for future refinement. From a public health perspective, the priority should not be precise quantification but rather a shift toward active case-finding to detect both asymptomatic patients and symptomatic patients who have not sought care, thereby disrupting hidden transmission chains and advancing the End TB goals.
{"title":"Estimating the contribution to transmission of asymptomatic tuberculosis from population-based genomic epidemiology studies.","authors":"Meng Li,Long Cai,Qian Gao","doi":"10.1080/22221751.2026.2640282","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640282","url":null,"abstract":"Asymptomatic tuberculosis (TB) poses a major challenge to global TB control. Quantifying its contribution to transmission remains a critical question. Although modelling studies have attempted to address this issue, empirical evidence from real-world settings is scarce. In this study, we estimated the contribution of asymptomatic TB to transmission in China using genomic epidemiology data from five population-based studies, encompassing 6,387 TB patients and 1,626 genomic-clustered patients. Transmission were classified as originating from either asymptomatic or symptomatic TB by comparing reported symptom onset dates with phybreak-inferred transmission timings. Across the study regions, 25.0%-51.3% of transmission was attributed to asymptomatic TB, indicating its substantial role in sustaining transmission. However, accurate estimation is hindered by the subjectivity of symptom reporting and reliance on passive case-finding. While this study likely underestimates the true contribution, it establishes a genomic epidemiology-based framework for future refinement. From a public health perspective, the priority should not be precise quantification but rather a shift toward active case-finding to detect both asymptomatic patients and symptomatic patients who have not sought care, thereby disrupting hidden transmission chains and advancing the End TB goals.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"45 1","pages":"2640282"},"PeriodicalIF":13.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383658","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}
BACKGROUNDHIV-1 CRF01_AE exhibits multiple distinct sub-subtypes (01_C1-C8) with different transmission dynamics across China. Understanding their geographical distribution, transmission patterns, and key affected populations is critical for optimizing targeted interventions.METHODSWe conducted a comprehensive molecular epidemiological study analyzing 4,011 partial pol sequences and demographic data from newly diagnosed CRF01_AE cases (2016-2019) in Shenyang (Northeast China) and Shenzhen (South China) by constructing the CRF01_AE molecular network in China (n = 6140). Sub-subtyping was performed using an online HIV subtyping tool and phylogenetic analysis. A molecular network was constructed based on genetic distance, and viral dispersal in large clusters (size≥10) in the network was assessed using Bayesian inference.RESULTS01_C5 (46.7%), 01_C4 (37.2%), 01_C1 (8.1%), 01_C2 (2.3%), 01_C3 (0.3%), and 01_C8 (<0.1%) were detected, with 01_C5 (73.7%) dominating in Shenyang, and 01_C4 (53.0%) in Shenzhen. Molecular network analysis revealed 24 large clusters, including 12 01_C5 clusters (64.7%) and 10 01_C4 clusters (28.5%). Notably, 01_C5 accounted for 75.9% of the mixed large clusters containing sequences from both cities. Bayesian phylodynamic analysis indicated one-way transmission of 01_C5 from Shenyang to Shenzhen was driven by middle-aged MSM (30-49 years old).CONCLUSIONOur findings provided a potential molecular epidemiological evidence for CRF01_AE transmission from Northeast China to South China, and highlighted the urgent need for targeted interventions focusing on middle-aged MSM to prevent cross-regional 01_C5 transmission. This study provided an example for applying traceability analysis based on the HIV molecular transmission network in guiding targeted public health interventions.
hiv -1 CRF01_AE表现出多个不同的亚型（01_C1-C8），在中国具有不同的传播动态。了解其地理分布、传播模式和主要受影响人群对于优化有针对性的干预措施至关重要。方法通过构建中国CRF01_AE分子网络（n = 6140），对沈阳（东北）和深圳（华南）2016-2019年新诊断CRF01_AE病例的4,011个部分pol序列和人口学数据进行全面的分子流行病学研究。使用在线HIV亚型分型工具和系统发育分析进行亚亚型分型。基于遗传距离构建分子网络，利用贝叶斯推理评估网络中病毒在大簇（≥10）中的扩散情况。结果共检出01_C5（46.7%）、01_C4（37.2%）、01_C1（8.1%）、01_C2（2.3%）、01_C3（0.3%）和01_C8(<0.1%)，其中沈阳以01_C5（73.7%）为主，深圳以01_C4（53.0%）为主。分子网络分析发现大簇属24个，其中01_C5簇属12个（64.7%），01_C4簇属10个（28.5%）。值得注意的是，在包含两个城市序列的混合大集群中，01_C5占75.9%。贝叶斯系统动力学分析表明，沈阳至深圳的01_C5单向传播主要由中年男男性行为者（30 ~ 49岁）驱动。结论本研究结果为CRF01_AE从东北向华南传播提供了潜在的分子流行病学证据，迫切需要针对中年MSM进行针对性干预，防止CRF01_AE跨区域传播。本研究为应用基于HIV分子传播网络的可追溯性分析指导有针对性的公共卫生干预提供了范例。
{"title":"Molecular footprints of a traveling epidemic: CRF01_AE-cluster 5 (01_C5) might spread across Northeast and South China via middle-aged MSM.","authors":"Wenxuan Yang,Bin Zhao,Mingming Kang,Minghui An,Wei Song,Xue Dong,Xin Li,Lu Wang,Jianmin Liu,Chenli Zheng,Lin Chen,Hao Li,Yan Zhang,Yongxia Gan,Wen Gan,Hui Zhang,Xiaoxu Han,Jin Zhao,Hong Shang","doi":"10.1080/22221751.2026.2637290","DOIUrl":"https://doi.org/10.1080/22221751.2026.2637290","url":null,"abstract":"BACKGROUNDHIV-1 CRF01_AE exhibits multiple distinct sub-subtypes (01_C1-C8) with different transmission dynamics across China. Understanding their geographical distribution, transmission patterns, and key affected populations is critical for optimizing targeted interventions.METHODSWe conducted a comprehensive molecular epidemiological study analyzing 4,011 partial pol sequences and demographic data from newly diagnosed CRF01_AE cases (2016-2019) in Shenyang (Northeast China) and Shenzhen (South China) by constructing the CRF01_AE molecular network in China (n = 6140). Sub-subtyping was performed using an online HIV subtyping tool and phylogenetic analysis. A molecular network was constructed based on genetic distance, and viral dispersal in large clusters (size≥10) in the network was assessed using Bayesian inference.RESULTS01_C5 (46.7%), 01_C4 (37.2%), 01_C1 (8.1%), 01_C2 (2.3%), 01_C3 (0.3%), and 01_C8 (<0.1%) were detected, with 01_C5 (73.7%) dominating in Shenyang, and 01_C4 (53.0%) in Shenzhen. Molecular network analysis revealed 24 large clusters, including 12 01_C5 clusters (64.7%) and 10 01_C4 clusters (28.5%). Notably, 01_C5 accounted for 75.9% of the mixed large clusters containing sequences from both cities. Bayesian phylodynamic analysis indicated one-way transmission of 01_C5 from Shenyang to Shenzhen was driven by middle-aged MSM (30-49 years old).CONCLUSIONOur findings provided a potential molecular epidemiological evidence for CRF01_AE transmission from Northeast China to South China, and highlighted the urgent need for targeted interventions focusing on middle-aged MSM to prevent cross-regional 01_C5 transmission. This study provided an example for applying traceability analysis based on the HIV molecular transmission network in guiding targeted public health interventions.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"5 1","pages":"2637290"},"PeriodicalIF":13.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383493","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 increasing emergence of vaccine antigen-deficient Bordetella pertussis (Bp) variants has raised concerns regarding disease control and prevention. Here, we characterized the pathogenicity and vaccine protection of circulating pertactin-deficient (PRN-), filamentous hemagglutinin-deficient (FHA-), and double-deficient (FHA-PRN-) Bp isolates. In vitro assays assessed bacterial proliferation, autoaggregation, adhesion to and invasion of A549 cells, associated cytokine responses in THP-1 cells, and cell death induction in both A549 and THP-1 cells. In vivo, the lung colonization, pulmonary immune responses, and the protection of three pertussis-containing vaccines against antigen-deficient isolates were investigated in a murine model. The PRN- isolate exhibited WT-like proliferation, adhesion, invasion, and lung colonization, and induced markedly enhanced pro-inflammatory responses and increased A549 cell death. The FHA- and FHA-PRN- isolates showed faster in vitro growth, reduced autoaggregation, adhesion, invasion, and THP-1 cell death levels, similar lung colonization, alongside a slight increase in inflammatory cytokine induction compared with the WT strain. Flow cytometric analysis revealed that the PRN- isolate induced a WT-like lung immune cell profile, whereas the FHA- and FHA-PRN- isolates induced a higher proportion of neutrophils, and FHA- infection was associated with reduced alveolar macrophage and dendritic cells. DTcP and DTaP vaccines provided distinct levels of protection against antigen-deficient isolates. Breakthrough infections were observed in 69.57% (16/23) vaccinated mice challenged with the FHA-PRN- strain. In conclusion, PRN and FHA deficiencies could alter some pertussis virulence-associated phenotypes and modulate host immune responses, thereby contributing to changes in vaccine protection.
{"title":"Pathogenicity and vaccine protection of circulating pertactin- and filamentous hemagglutinin-deficient Bordetella pertussis strains.","authors":"Hanying Dai,Xiuwen Sui,Jie Che,Chunying Zhang,Jiayu Zhao,Jie Li,Bohan Chen,Luyao Guo,Dongshan Yan,Hairui Wang,Xueping Liu,Li Xu,Yuan Gao,Aiping Qin,Tao Zhu,Maojun Zhang,Zhujun Shao","doi":"10.1080/22221751.2026.2640283","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640283","url":null,"abstract":"The increasing emergence of vaccine antigen-deficient Bordetella pertussis (Bp) variants has raised concerns regarding disease control and prevention. Here, we characterized the pathogenicity and vaccine protection of circulating pertactin-deficient (PRN-), filamentous hemagglutinin-deficient (FHA-), and double-deficient (FHA-PRN-) Bp isolates. In vitro assays assessed bacterial proliferation, autoaggregation, adhesion to and invasion of A549 cells, associated cytokine responses in THP-1 cells, and cell death induction in both A549 and THP-1 cells. In vivo, the lung colonization, pulmonary immune responses, and the protection of three pertussis-containing vaccines against antigen-deficient isolates were investigated in a murine model. The PRN- isolate exhibited WT-like proliferation, adhesion, invasion, and lung colonization, and induced markedly enhanced pro-inflammatory responses and increased A549 cell death. The FHA- and FHA-PRN- isolates showed faster in vitro growth, reduced autoaggregation, adhesion, invasion, and THP-1 cell death levels, similar lung colonization, alongside a slight increase in inflammatory cytokine induction compared with the WT strain. Flow cytometric analysis revealed that the PRN- isolate induced a WT-like lung immune cell profile, whereas the FHA- and FHA-PRN- isolates induced a higher proportion of neutrophils, and FHA- infection was associated with reduced alveolar macrophage and dendritic cells. DTcP and DTaP vaccines provided distinct levels of protection against antigen-deficient isolates. Breakthrough infections were observed in 69.57% (16/23) vaccinated mice challenged with the FHA-PRN- strain. In conclusion, PRN and FHA deficiencies could alter some pertussis virulence-associated phenotypes and modulate host immune responses, thereby contributing to changes in vaccine protection.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"52 1","pages":"2640283"},"PeriodicalIF":13.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383494","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}
Current antiviral therapies for orthopoxviruses face critical challenges, including limited efficacy and significant toxicity, which impede outbreak containment and clinical management. Here, we identify lactoferrin as a potent antiviral agent against multiple orthopoxvirus strains. Combination administration of lactoferrin with brincidofovir or tecovirimat demonstrated additive efficacy, suggesting a potential clinical strategy to reduce individual drug toxicity. Mechanistically, lactoferrin blocks viral entry by competitively binding to heparan sulphate proteoglycans (HSPGs). It also suppresses viral replication by regulating host antiviral pathways, including down-regulating cytokines and upregulating TGF-β-dependent antiviral signalling pathways. We identify TGFBI as a virus-responsive target regulated by lactoferrin. Lactoferrin treatment restores TGFBI expression and activates downstream MAPK/ERK and JAK2/STAT3 signalling cascades, leading to enhanced interferon production and interferon-stimulated gene (ISG) expression. In a murine vaccinia virus (VACV) infection model, lactoferrin treatment reduced lung viral loads and histological damage. These results underscore lactoferrin's distinctive dual antiviral mechanism and highlight its translational potential as a safe and cost-effective prophylactic or therapeutic agent. It is particularly beneficial for immunocompromised populations in resource-limited settings during orthopoxvirus outbreaks.
{"title":"Lactoferrin blocks orthopoxvirus entry via heparan sulphate and regulates host antiviral pathways.","authors":"Lili Tian,Hongbo Qin,Sha Li,Mengjie Zhang,Lu Zhuang,Bixia Hong,Ke Liu,Maochen Li,Siyue Li,Yaxin Wang,Lihua Song,Yang Liu,Yun Wang,Huiyu Liu,Yigang Tong,Huahao Fan","doi":"10.1080/22221751.2026.2631205","DOIUrl":"https://doi.org/10.1080/22221751.2026.2631205","url":null,"abstract":"Current antiviral therapies for orthopoxviruses face critical challenges, including limited efficacy and significant toxicity, which impede outbreak containment and clinical management. Here, we identify lactoferrin as a potent antiviral agent against multiple orthopoxvirus strains. Combination administration of lactoferrin with brincidofovir or tecovirimat demonstrated additive efficacy, suggesting a potential clinical strategy to reduce individual drug toxicity. Mechanistically, lactoferrin blocks viral entry by competitively binding to heparan sulphate proteoglycans (HSPGs). It also suppresses viral replication by regulating host antiviral pathways, including down-regulating cytokines and upregulating TGF-β-dependent antiviral signalling pathways. We identify TGFBI as a virus-responsive target regulated by lactoferrin. Lactoferrin treatment restores TGFBI expression and activates downstream MAPK/ERK and JAK2/STAT3 signalling cascades, leading to enhanced interferon production and interferon-stimulated gene (ISG) expression. In a murine vaccinia virus (VACV) infection model, lactoferrin treatment reduced lung viral loads and histological damage. These results underscore lactoferrin's distinctive dual antiviral mechanism and highlight its translational potential as a safe and cost-effective prophylactic or therapeutic agent. It is particularly beneficial for immunocompromised populations in resource-limited settings during orthopoxvirus outbreaks.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"250 1","pages":"2631205"},"PeriodicalIF":13.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368286","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 : 2026-03-06DOI: 10.1080/22221751.2026.2637280
Pallavi Singh,Karel Estrada,Luis Miguel Gonzalez,Ricardo Grande,Sergio Sánchez-Prieto,Emmanuel Cornillot,Omar Harb,Alejandro Sanchez-Flores,Estrella Montero,Karine G Le Roch,Stefano Lonardi,Choukri Ben Mamoun
A zoonotic Babesia species previously referred to as Babesia sp. MO1 is formally described and named here as Babesia hegotelforum sp. nov. This taxon is distinct from Babesia divergens based on genome-wide sequence divergence, phylogenetic placement, host associations, and clinical presentation. The parasite infects erythrocytes of humans, and eastern cottontail rabbits (Sylvilagus floridanus), and is transmitted by Ixodes dentatus. The holotype consists of a Giemsa-stained thin blood smear and cryopreserved infected erythrocytes from the cloned isolate BML-Bh-B12 at ≤10 passages in continuous in vitro culture. Paratype material includes five additional clones (BML-Bh-H1, BML-Bh-F12, BML-Bh-H6, BML-Bh-A3, and BML-Bh-F1) derived from BEI Resources strain NR-50441, along with the original mixed isolate NR-50441. This species description meets the requirements of the International Code of Zoological Nomenclature and establishes Babesia hegotelforum sp. nov. as a distinct species of clinical and epidemiological significance in North America.
{"title":"Babesia hegotelforum sp. nov., a zoonotic Babesia species previously referred to as Babesia sp. MO1.","authors":"Pallavi Singh,Karel Estrada,Luis Miguel Gonzalez,Ricardo Grande,Sergio Sánchez-Prieto,Emmanuel Cornillot,Omar Harb,Alejandro Sanchez-Flores,Estrella Montero,Karine G Le Roch,Stefano Lonardi,Choukri Ben Mamoun","doi":"10.1080/22221751.2026.2637280","DOIUrl":"https://doi.org/10.1080/22221751.2026.2637280","url":null,"abstract":"A zoonotic Babesia species previously referred to as Babesia sp. MO1 is formally described and named here as Babesia hegotelforum sp. nov. This taxon is distinct from Babesia divergens based on genome-wide sequence divergence, phylogenetic placement, host associations, and clinical presentation. The parasite infects erythrocytes of humans, and eastern cottontail rabbits (Sylvilagus floridanus), and is transmitted by Ixodes dentatus. The holotype consists of a Giemsa-stained thin blood smear and cryopreserved infected erythrocytes from the cloned isolate BML-Bh-B12 at ≤10 passages in continuous in vitro culture. Paratype material includes five additional clones (BML-Bh-H1, BML-Bh-F12, BML-Bh-H6, BML-Bh-A3, and BML-Bh-F1) derived from BEI Resources strain NR-50441, along with the original mixed isolate NR-50441. This species description meets the requirements of the International Code of Zoological Nomenclature and establishes Babesia hegotelforum sp. nov. as a distinct species of clinical and epidemiological significance in North America.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"127 1","pages":"2637280"},"PeriodicalIF":13.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368285","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}
Chikungunya virus (CHIKV), an emerging mosquito-borne alphavirus, induces debilitating polyarthralgia and myositis with no licensed specific therapeutic drugs. This study investigates the virological, immunological, and pathological consequences of targeting glycolysis and glutaminolysis during CHIKV infection. In vitro, either glucose/glutamine deprivation, or pharmacological inhibition by 2DG/DON significantly suppressed viral replication in mammalian cell lines. In vivo, however, differential tissue biodistribution dictated that neither inhibitor reduced viral loads in serum or foot tissues of acute infected mice following footpad inoculation with 10⁴ PFU CHIKV. Strikingly, DON, but not 2DG, abolished histopathological manifestations of myositis and inflammatory infiltration despite comparable viral burdens. Mechanistically, DON-mediated tissue protection was related to dual immunomodulation. DON significantly depleted splenic innate immune cells, including monocytes and macrophages, which play roles in driving tissue inflammatory infiltration cascades. Meanwhile, DON inhibited CD4 + and CD8+ T cell effector programmes, resulting in suppressed activation marker (CD44) expression and effector cell differentiation (decreased effector: naive ratio and TEM: TCM balance). The proliferative capacity (Ki-67 + cells), polyfunctional cytokine responses (IFN-γ+, TNF-α and IL-17 + cells) and cytotoxicity potential (CD107a + cells) of CD4 + and CD8+ T cells were significantly impaired by DON injection. Crucially, glutaminolysis inhibition uncoupled immunopathology from viral containment, attenuating tissue damaging immunity while preserving baseline antiviral competence. Collectively, these findings establish host glutamine metabolism as a pharmacologically tractable target for alphavirus-induced arthritis, demonstrating that selective immunometabolic modulation resolves the severe acute inflammatory pathology.
{"title":"Glutamine antagonist DON attenuates chikungunya virus-induced myositis by suppressing inflammatory activation in a murine model.","authors":"Xinyu Zhang,Yue Zhang,Jiarui Huang,Zhiyong Ma,Hu Yan,Maohua Zhong,Jingyi Yang,Fengjiao Hu,Mengliu Zeng,Mengji Lu,Huimin Yan,Ejuan Zhang","doi":"10.1080/22221751.2026.2622213","DOIUrl":"https://doi.org/10.1080/22221751.2026.2622213","url":null,"abstract":"Chikungunya virus (CHIKV), an emerging mosquito-borne alphavirus, induces debilitating polyarthralgia and myositis with no licensed specific therapeutic drugs. This study investigates the virological, immunological, and pathological consequences of targeting glycolysis and glutaminolysis during CHIKV infection. In vitro, either glucose/glutamine deprivation, or pharmacological inhibition by 2DG/DON significantly suppressed viral replication in mammalian cell lines. In vivo, however, differential tissue biodistribution dictated that neither inhibitor reduced viral loads in serum or foot tissues of acute infected mice following footpad inoculation with 10⁴ PFU CHIKV. Strikingly, DON, but not 2DG, abolished histopathological manifestations of myositis and inflammatory infiltration despite comparable viral burdens. Mechanistically, DON-mediated tissue protection was related to dual immunomodulation. DON significantly depleted splenic innate immune cells, including monocytes and macrophages, which play roles in driving tissue inflammatory infiltration cascades. Meanwhile, DON inhibited CD4 + and CD8+ T cell effector programmes, resulting in suppressed activation marker (CD44) expression and effector cell differentiation (decreased effector: naive ratio and TEM: TCM balance). The proliferative capacity (Ki-67 + cells), polyfunctional cytokine responses (IFN-γ+, TNF-α and IL-17 + cells) and cytotoxicity potential (CD107a + cells) of CD4 + and CD8+ T cells were significantly impaired by DON injection. Crucially, glutaminolysis inhibition uncoupled immunopathology from viral containment, attenuating tissue damaging immunity while preserving baseline antiviral competence. Collectively, these findings establish host glutamine metabolism as a pharmacologically tractable target for alphavirus-induced arthritis, demonstrating that selective immunometabolic modulation resolves the severe acute inflammatory pathology.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"101 1","pages":"2622213"},"PeriodicalIF":13.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368287","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}
Tick-borne encephalitis (TBE) is a potentially life-threatening viral disease with rising incidence in Europe. This retrospective study investigates the incidence, clinical course, and long-term outcome of TBE in Åland, a region endemic for the disease, following the introduction of a TBE vaccination programme in 2006.All patients diagnosed with TBE in Åland between 2006 and 2023, in accordance with the diagnostic criteria established by the European Centre for Disease Prevention and Control (ECDC), were included in the study. A review of medical records was conducted, and epidemiological and laboratory data were systematically collected. Disease severity and clinical outcome were assessed.TBE was diagnosed in 145 patients (66% male; median age 53 years; 10% children <18 years). The median TBE incidence was 29/100,000/year. Primary care was the first point of contact in 48% of cases. Of all patients, 72 (50%) were unvaccinated, 46 (32%) incompletely vaccinated and 20 (14%) completely vaccinated. Fifty-seven (39%) were diagnosed with meningitis and 88 (61%) with meningoencephalitis. Overall, 117/145 (81%) patients were hospitalised and 13/145 (9%) required intensive care. Severity of disease correlated with increasing age. Two fatalities occurred.Unlike neighbouring regions, Åland did not experience an increase in TBE incidence, likely due to the implementation of the vaccination programme. Most disease courses were monophasic and occurred in unvaccinated individuals. Surprisingly, a significant number of breakthrough infections were observed, particularly among those with incomplete vaccination, who more frequently developed severe disease. However, at two-year follow-up, 86% of patients were considered clinically recovered.
{"title":"Tick-borne encephalitis in the Åland Islands, Finland: incidence and disease course since the implementation of a general TBE vaccination programme.","authors":"Jessica Tikkala,Christian Jansson,Gunilla Häggblom,Malin Ringbom,Mathias Grunér,Dag Nyman,Marjaana Pitkäpaasi,Johanna Sjöwall,Marika Nordberg","doi":"10.1080/22221751.2026.2640705","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640705","url":null,"abstract":"Tick-borne encephalitis (TBE) is a potentially life-threatening viral disease with rising incidence in Europe. This retrospective study investigates the incidence, clinical course, and long-term outcome of TBE in Åland, a region endemic for the disease, following the introduction of a TBE vaccination programme in 2006.All patients diagnosed with TBE in Åland between 2006 and 2023, in accordance with the diagnostic criteria established by the European Centre for Disease Prevention and Control (ECDC), were included in the study. A review of medical records was conducted, and epidemiological and laboratory data were systematically collected. Disease severity and clinical outcome were assessed.TBE was diagnosed in 145 patients (66% male; median age 53 years; 10% children <18 years). The median TBE incidence was 29/100,000/year. Primary care was the first point of contact in 48% of cases. Of all patients, 72 (50%) were unvaccinated, 46 (32%) incompletely vaccinated and 20 (14%) completely vaccinated. Fifty-seven (39%) were diagnosed with meningitis and 88 (61%) with meningoencephalitis. Overall, 117/145 (81%) patients were hospitalised and 13/145 (9%) required intensive care. Severity of disease correlated with increasing age. Two fatalities occurred.Unlike neighbouring regions, Åland did not experience an increase in TBE incidence, likely due to the implementation of the vaccination programme. Most disease courses were monophasic and occurred in unvaccinated individuals. Surprisingly, a significant number of breakthrough infections were observed, particularly among those with incomplete vaccination, who more frequently developed severe disease. However, at two-year follow-up, 86% of patients were considered clinically recovered.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"100 1","pages":"2640705"},"PeriodicalIF":13.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346438","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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