Patricia L Earl,Jeffrey L Americo,Sara Reynolds,Wei Xiao,Catherine Cotter,Bernard Moss
{"title":"A Functional Approach to Analyze the Genetic Basis for Differences in Virulence of Monkeypox Virus Clades.","authors":"Patricia L Earl,Jeffrey L Americo,Sara Reynolds,Wei Xiao,Catherine Cotter,Bernard Moss","doi":"10.1080/22221751.2025.2456144","DOIUrl":"https://doi.org/10.1080/22221751.2025.2456144","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"1 1","pages":"2456144"},"PeriodicalIF":13.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989710","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}
{"title":"Phages adapt to recognize an O-antigen polysaccharide site by mutating the 'backup' tail protein ORF59, enabling reinfection of phage-resistant Klebsiella pneumoniae.","authors":"Ping Li,Wenjie Ma,Jun Cheng,Cuixing Zhan,Hongzhou Lu,Jiayin Shen,Xin Zhou","doi":"10.1080/22221751.2025.2455592","DOIUrl":"https://doi.org/10.1080/22221751.2025.2455592","url":null,"abstract":"Phages demonstrate remarkable promise as antimicrobial agents against antibiotic-resistant bacteria. However, the emergence of phage-resistant strains poses challenges to their effective application. In this paper, we presented the isolation of a phage adaptive mutant that demonstrated enhanced and sustained antibacterial efficacy through the co-evolution of Klebsiella pneumoniae (K. pneumoniae) 111-2 and phage ZX1Δint in vitro. Our experiments revealed that phage ZX1Δint successfully completed the adsorption phase by binding to the host surface, specifically targeting the capsular polysaccharide (CPS) receptor via the primary receptor-binding protein (RBP) ORF60 and the auxiliary RBP ORF59. Upon exposure to phage predation, mutations in genes wbaP, wbaZ or wzc, which encode the synthesis of the CPS, conferred resistance by reducing phage adsorption. In response to these host defense mechanisms, the adaptive mutant phages have evolved to utilize an alternative binding site located on an O-antigen site of lipopolysaccharide (LPS) through a mutation in the backup RBP ORF59. This evolutionary change enabled the phages to reinfect previously phage-resistant strains. Notably, the adaptive mutant phage PR2 carrying the ORF59 mutation Q777R, demonstrated the capacity to infect both wild-type and resistant strains, exhibiting prolonged antimicrobial activity against the wild strains. In conclusion, our findings elucidated a complex phage-host adsorption-antagonism mechanism characterized by mutation-driven alterations in phage receptor recognition. This work contributes to a deeper understanding of phage adaptability and highlights the potential for phages to combat phage-resistant bacteria through an in vitro evolutionary approach.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"7 1","pages":"2455592"},"PeriodicalIF":13.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988931","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}
{"title":"Vδ2 T-cells response in people with Mpox infection: a three-month longitudinal assessment.","authors":"Eleonora Cimini,Eleonora Tartaglia,Francesco Messina,Andrea Coppola,Valentina Mazzotta,Massimo Tempestilli,Giulia Matusali,Stefania Notari,Annalisa Mondi,Gianluca Prota,Alessandra Oliva,Carla Fontana,Enrico Girardi,Fabrizio Maggi,Andrea Antinori","doi":"10.1080/22221751.2025.2455585","DOIUrl":"https://doi.org/10.1080/22221751.2025.2455585","url":null,"abstract":"The first evidence that Orthopoxvirus induced the expansion in vivo and the recall of effector innate Vδ2 T-cells was described in a macaque model. Although, an engagement of αβ T-cells specific response in patients infected with human monkeypox (Mpox) was demonstrated, little is known about the role of γδ T-cells during Mpox infection. IFN-γ-producing γδ T-cells in the resistance to poxviruses may a key role in inducing a protective type 1 memory immunity. We analyzed the kinetics of Vδ2 T-cell response from the acute phase up to three months after Mpox infection. Fourteen MSM subjects (5 PWH, 35.7%) were enrolled in a longitudinal study from May to July 2022. Blood samples were collected in the early phase of infection (T1, T2) and at 3 months (T3M) post-symptom onset. Vδ2 T-cell profiles (CD45RA/CCR7), activation/exhaustion markers (CD38/HLA-DR/CD57/PD-1/TIM-3), cytokine production (IFN-γ/TNF-α) and CD107a expression were assessed by multiparametric flow cytometry. Ten healthy donors (HD) were used as a control group. At T1, Vδ2 T-cell frequency of patients decreased, and effector memory Vδ2 T-cells increased with respect to HD. Activation/exhaustion markers were higher than HD. Vδ2 functionality decreased at T1 related to HD, and it was associated with CD38 and HLA-DR higher expression as well as TIM-3. Vδ2 T-cells restored their profile at T3M. The presence of effector/activated Vδ2 T-cells in the early stages of Mpox infection and their capability to activate quickly, producing pro-inflammatory cytokines, may be useful to enhance the early adaptive response to human Mpox, maintaining a protective memory/effector T-cell response.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"27 1","pages":"2455585"},"PeriodicalIF":13.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988473","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}
{"title":"Ecological Drivers of Evolution of Swine Influenza in the United States: A Review.","authors":"Varun Goel,Jessica Ding,Bijaya Hatuwal,Emily Giri,Thomas J Deliberto,Jim Lowe,Richard Webby,Michael Emch,Xiu-Feng Wan","doi":"10.1080/22221751.2025.2455598","DOIUrl":"https://doi.org/10.1080/22221751.2025.2455598","url":null,"abstract":"AbstractInfluenza A viruses (IAVs) pose a major public health threat due to their wide host range and pandemic potential. Pigs have been proposed as \"mixing vessels\" for avian, swine, and human IAVs, significantly contributing to influenza ecology. In the United States, IAVs are enzootic in commercial swine farming operations, with numerous genetic and antigenic IAV variants having emerged in the past two decades. However, the dynamics of intensive swine farming systems and their interactions with ecological factors influencing IAV evolution have not been systematically analyzed. This review examines the evolution of swine IAVs in commercial farms, highlighting the role of multilevel ecological factors. A total of 61 articles published after 2000 were reviewed, with most studies conducted after 2009 in Midwestern US, followed by Southeast and South-central US. The findings reveal that ecological factors at multiple spatial scales, such as regional transportation networks, interconnectedness of swine operations, farm environments, and presence of high-density, low-genetic diversity herds, can facilitate virus transmission and enhance virus evolution. Additionally, interactions at various interfaces, such as between commercial swine and feral swine, humans, or wild birds contribute to the increase in genetic diversity of swine IAVs. The review underscores the need for comprehensive studies and improved data collection to better understand the ecological dynamics influencing swine IAV evolution. This understanding is crucial for mitigating disease burdens in swine production and reducing the risk of zoonotic influenza outbreaks.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"30 1","pages":"2455598"},"PeriodicalIF":13.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988930","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}
{"title":"Isoleucine at position 137 of Hemagglutinin acts as a Mammalian adaptation marker of H9N2 Avian influenza virus.","authors":"Weiwei Ma,Chenyang Ren,Lin Shi,Bo Meng,Yali Feng,Ying Zhang","doi":"10.1080/22221751.2025.2455597","DOIUrl":"https://doi.org/10.1080/22221751.2025.2455597","url":null,"abstract":"AbstractThe H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified ten H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference. A series of reassortants between CKLN/07 and CKLN/17 were generated and their chick embryo lethality was assessed. We found that the isoleucine (I) residue at position 137 (H3 numbering) in the hemagglutinin (HA) was responsible for the chick embryo lethality of the H9N2 virus. Further studies revealed that the threonine (T) to I mutation at HA position 137 enhanced viral replication in vitro and in vivo. Moreover, the HA-T137I substitution in H9N2 avian influenza virus increased the guinea pig transmission efficiency. We also found that the HA-T137I substitution was critical for α2,6-linked sialic acid binding preference and HA activation and stability of H9N2 virus. Our findings demonstrated that HA-137I is a key molecular marker for mammalian adaptation of H9N2 AIV.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"55 1","pages":"2455597"},"PeriodicalIF":13.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988932","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}
{"title":"Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant Serratia marcescens-induced pulmonary infection.","authors":"Xiangke Duan,Wenfeng Liu,Yanyu Xiao,Man Rao,Liyin Ji,Xiaofu Wan,Shuhong Han,Zixun Lin,Haichen Liu,Peifen Chen,Kun Qiao,Mingbin Zheng,Jiayin Shen,Yang Zhou,Tetsuya Asakawa,Minfeng Xiao,Hongzhou Lu","doi":"10.1080/22221751.2025.2451048","DOIUrl":"https://doi.org/10.1080/22221751.2025.2451048","url":null,"abstract":"Serratia marcescens (S. marcescens) commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for S. marcescens infection. This study was conducted to explore the feasibility of phage application in treating refractory S. marcescens infection by collaborating with a 59-year-old male patient with a pulmonary infection of multidrug-resistant S. marcescens. Our experiments included three domains: i) selection of the appropriate phage, ii) verification of the efficacy and safety of the selected phage, iii) confirmation of phage-bacteria interactions. Our results showed that phage Spe5P4 is appropriate for S. marcescens infection. Treatment with phage Spe5P4 showed good efficacy, manifested as amelioration of symptoms, hydrothorax examinations, and chest computed tomography findings. Phage treatment did not worsen hepatic and renal function, immunity-related indices, or indices of routine blood examination. It did not induce or deteriorate drug resistance of the involved antibiotics. Importantly, no adverse events were reported during the treatment or follow-up periods. Thus, phage treatment showed satisfactory safety. Finally, we found that phage treatment did not increase the bacterial load, cytotoxicity, virulence, or phage resistance of S. marcescens, indicating satisfactory phage-bacteria interactions between Spe5P4 and S. marcescens, which are useful for the future application of phage Spe5P4 against S. marcescens. This work provides evidence and a working basis for further application of phage Spe5P4 in treating refractory S. marcescens infections. We also provided a methodological basis for investigating clinical application of phage treatment against multidrug-resistant bacterial infections in the future.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"5 1","pages":"2451048"},"PeriodicalIF":13.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988474","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}
{"title":"Genotypic Variations and Clinical Implications of JEV-Associated Peripheral Nerve Injury: A Commentary on Multicenter Findings from High-Endemic Regions.","authors":"Liangping Zhang, Lei Pan, Rongqi Cao","doi":"10.1080/22221751.2024.2449073","DOIUrl":"https://doi.org/10.1080/22221751.2024.2449073","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2449073"},"PeriodicalIF":8.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946575","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}
Jian Sun,Lei Qian,Delong Li,Xiurong Wang,Hong Zhou,Cixiu Li,Edward C Holmes,Jianke Wang,Juan Li,Weifeng Shi
{"title":"Concurrent Severe Fever with Thrombocytopenia Syndrome Virus Outbreaks on Multiple Fox Farms, China, 2023.","authors":"Jian Sun,Lei Qian,Delong Li,Xiurong Wang,Hong Zhou,Cixiu Li,Edward C Holmes,Jianke Wang,Juan Li,Weifeng Shi","doi":"10.1080/22221751.2024.2447610","DOIUrl":"https://doi.org/10.1080/22221751.2024.2447610","url":null,"abstract":"The role of farmed animals in the viral spillover from wild animals to humans is of growing importance. Between July and September of 2023 infectious disease outbreaks were reported on six Arctic fox (Vulpes lagopus) farms in Shandong and Liaoning provinces, China, which lasted for 2-3 months and resulted in tens to hundreds of fatalities per farm. Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was identified in tissue/organ and swab samples from all the 13 foxes collected from these farms. These animals exhibited loss of appetite and weight loss, finally resulting in death. In autopsy and histopathology, prominently enlarged spleens and extensive multi-organ hemorrhage were observed, respectively, indicating severe systemic effects. Viral loads were detected in various tissues/organs, including brains from 12 of the 13 foxes. SFTSV was also detected in serum, anal swabs, as well as in environmental samples, including residual food in troughs used by dying foxes in two follow-up studies at two farms. The 13 newly sequenced SFTSV genomes shared >99.43% nucleotide identity with human strains from China. Phylogenetic analyses showed that the 13 sequences belonged to three genotypes, and that two sequences from Liaoning were genomic reassortants, indicative of multiple sources and introduction events. This study provides the first evidence of SFTSV infection, multi-tissue tropism, and pathogenicity in farmed foxes, representing an expanded virus host range. However, the widespread circulation of different genotypes of SFTSV in farmed animals from different provinces and the diverse transmission routes, highlight its increasing and noticeable public health risk in China.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"160 1","pages":"2447610"},"PeriodicalIF":13.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887774","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}
Lennart Kämper,Ida Kuhl,Melina Vallbracht,Thomas Hoenen,Uwe Linne,Axel Weber,Petr Chlanda,Michael Kracht,Nadine Biedenkopf
{"title":"To be or not to be phosphorylated: Understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56.","authors":"Lennart Kämper,Ida Kuhl,Melina Vallbracht,Thomas Hoenen,Uwe Linne,Axel Weber,Petr Chlanda,Michael Kracht,Nadine Biedenkopf","doi":"10.1080/22221751.2024.2447612","DOIUrl":"https://doi.org/10.1080/22221751.2024.2447612","url":null,"abstract":"Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal disordered region. This study investigates NP's role in VP30 dephosphorylation and transcription activation, focusing on the spatial requirements of NP's binding sites. Increasing the distance between PP2A-B56 and VP30 at the NP interface revealed that close spatial and orientational contact is necessary for efficient VP30 dephosphorylation and viral transcription. Longer distances were lethal for recombinant EBOV except when a compensatory mutation, NP-T603I, occurred. This mutation, located between the NP binding sites for PP2A-B56 and VP30, fully restored functionality. Mass spectrometry showed that T603 is phosphorylated in recEBOV-NPwt virions. Mutational analysis indicated that T603I facilitates VP30 dephosphorylation in otherwise lethal recEBOV and that dynamic phosphorylation of NP-T603 is important for efficient primary viral transcription in the WT context. These findings emphasize the critical and evolutionarily pressured interplay between VP30 and PP2A-B56 within the NP C-terminal disordered region and highlight the important role of NP on the regulation of viral transcription during the EBOV life cycle.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"32 1","pages":"2447612"},"PeriodicalIF":13.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887772","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}
{"title":"The Prevalence of Low-level Viraemia and Its Association with Virological Failure in People Living With HIV: A Systematic Review and Meta-Analysis.","authors":"Shengnan Zhao,Wenjing Wang,Sibo Li,Jiaze He,Wenshan Duan,Zhen Fang,Xiaoran Ma,Zhen Li,Caiping Guo,Wen Wang,Hao Wu,Tong Zhang,Xiaojie Huang","doi":"10.1080/22221751.2024.2447613","DOIUrl":"https://doi.org/10.1080/22221751.2024.2447613","url":null,"abstract":"Low-level viraemia (LLV) following antiretroviral therapy (ART) in people living with HIV (PLWH) has not received sufficient attention. To the determine the prevalence of LLV and its association with virological failure (VF), we systematically reviewed evidence-based interventions for PLWH. We searched PubMed, the Cochrane Library, Embase, and Web of Science from inception to 22 May 2024. Cohorts with samples sizes smaller than 1000 in size were excluded. Data from 16 cohort studies, encompassing 1,349,306 PLWH, revealed a pooled prevalence of LLV of 13.81%. Relative risk (RR) and 95% confidence intervals (CI) identified the following risk factors for LLV: viral load (VL) ≥ 105 copies/mL at baseline (1.79, 1.11-2.88), AIDS-defined illness at baseline (1.24, 1.10-1.40), and protease inhibitor-based regimen at ART initiation (1.53, 1.45-1.62) are the risk factors for LLV. Conversely, CD4 count ≥200 cells/μL at baseline (0.90, 0.82-0.98), non-nucleoside reverse transcriptase inhibitor-based regimen (0.81, 0.68-0.96) and the integrase strand transfer inhibitor (INSTI)-based regimen (0.60, 0.42-0.85) were associated with a reduced risk of LLV. Pooling the adjusted hazard ratio (aHR) and the 95% CI, we found that LLV increased the risk of VF with rising VL among 96,711 PLWH (aHR 2.77, 95% CI 2.03-3.76) and increased the risk of all-cause mortality at high VL levels among 14,229 PLWH (aHR 1.66, 95% CI 1.16-2.37). Therefore, the prevalence of LLV in PLWH should not be overlooked. This study aims to guide better management strategies to improve clinical outcomes in patients with LLV.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"64 1","pages":"2447613"},"PeriodicalIF":13.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887771","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}