Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106638
Na Liu , Yanmei Li , Zhouyu Wu , Wenfei Qiao , Qianqian Zheng , Jing Zhuo , Yangzi Liu , Mengjie Lin , Ying Fu , Jiugang Zhao
Objective
Mosquito saliva can facilitate arboviral infection, yet whether host antibodies to salivary proteins modulate dengue virus (DENV) infection remains unclear. To test whether antibodies induced by Aedes albopictus salivary proteins (AaSP) enhance DENV infection when AaSP is present.
Methods
We used RAW264.7 cells and BALB/c mice; generated anti-AaSP antisera; co-incubated DENV with AaSP; quantified NS1 mRNA, envelope protein, and cytopathic effects (CPE); and assessed tissue pathology. We compared female- versus male-derived AaSP and antisera, performed proteomics, tested recombinant Obp1 and D7L, purified IgG, and evaluated papain digestion and Fcγ receptor (anti-CD16/32, clone 2.4G2) blockade.
Results
Antiserum with AaSP increased DENV infection in vitro and aggravated pathology in vivo. Repeated A. albopictus bites induced anti-AaSP antibodies and led to more severe disease after infection with AaSP-preincubated virus. Only female-AaSP antisera enhanced infection; proteomics showed sex-distinct salivary profiles. Obp1 and D7L enhanced infection with antiserum. Purified IgG reproduced the increase, which was lost after papain digestion or FcγR blockade.
Conclusion
Anti-AaSP IgG can increase DENV infection in the presence of AaSP. These findings add to understanding of DENV pathogenesis and may help inform future exploration of prevention targets.
{"title":"Antibodies to female Aedes albopictus salivary proteins promote dengue virus infection with salivary proteins","authors":"Na Liu , Yanmei Li , Zhouyu Wu , Wenfei Qiao , Qianqian Zheng , Jing Zhuo , Yangzi Liu , Mengjie Lin , Ying Fu , Jiugang Zhao","doi":"10.1016/j.jinf.2025.106638","DOIUrl":"10.1016/j.jinf.2025.106638","url":null,"abstract":"<div><h3>Objective</h3><div>Mosquito saliva can facilitate arboviral infection, yet whether host antibodies to salivary proteins modulate dengue virus (DENV) infection remains unclear. To test whether antibodies induced by <em>Aedes albopictus</em> salivary proteins (AaSP) enhance DENV infection when AaSP is present.</div></div><div><h3>Methods</h3><div>We used RAW264.7 cells and <em>BALB/c</em> mice; generated anti-AaSP antisera; co-incubated DENV with AaSP; quantified NS1 mRNA, envelope protein, and cytopathic effects (CPE); and assessed tissue pathology. We compared female- versus male-derived AaSP and antisera, performed proteomics, tested recombinant Obp1 and D7L, purified IgG, and evaluated papain digestion and Fcγ receptor (anti-CD16/32, clone 2.4G2) blockade.</div></div><div><h3>Results</h3><div>Antiserum with AaSP increased DENV infection in vitro and aggravated pathology in vivo. Repeated <em>A. albopictus</em> bites induced anti-AaSP antibodies and led to more severe disease after infection with AaSP-preincubated virus. Only female-AaSP antisera enhanced infection; proteomics showed sex-distinct salivary profiles. Obp1 and D7L enhanced infection with antiserum. Purified IgG reproduced the increase, which was lost after papain digestion or FcγR blockade.</div></div><div><h3>Conclusion</h3><div>Anti-AaSP IgG can increase DENV infection in the presence of AaSP. These findings add to understanding of DENV pathogenesis and may help inform future exploration of prevention targets.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106638"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106648
Yangyi Zhang , Danni Li , Jiazhen Liu , Yuan Jiang , Xin Shen , Biao Xu
Objectives
Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear.
Methods
A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022–2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform.
Results
Among 3496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis.
Conclusion
Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.
{"title":"Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: An EHR-based case-control study using whole-genome sequencing","authors":"Yangyi Zhang , Danni Li , Jiazhen Liu , Yuan Jiang , Xin Shen , Biao Xu","doi":"10.1016/j.jinf.2025.106648","DOIUrl":"10.1016/j.jinf.2025.106648","url":null,"abstract":"<div><h3>Objectives</h3><div>Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear.</div></div><div><h3>Methods</h3><div>A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022–2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform.</div></div><div><h3>Results</h3><div>Among 3496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis.</div></div><div><h3>Conclusion</h3><div>Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106648"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106642
Jing-ying Zhan , Luo Ren , Cheng-kai Li , Ling Zhong , Qiao-ping Wu , Run Wang , Da-peng Chen , Xiao Chen , Kang-yi Ren , Zheng-rong Chen , Zhe-min Zhou , Enmei Liu , Hong Tang
Mycoplasma pneumoniae (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with M. pneumoniae. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were M. pneumoniae mono-infected at hospitalization, and showed an expansion of both effector and memory CD8+ T cells, with exhausted KLRG1hi CD8+ T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM+ plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8+ T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated M. pneumoniae colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.
{"title":"Exhausted KLRG1hi CD8+ T and pathogenic GZMA+ Th17 cells are associated with the mild Mycoplasma pneumoniae pneumonia in children","authors":"Jing-ying Zhan , Luo Ren , Cheng-kai Li , Ling Zhong , Qiao-ping Wu , Run Wang , Da-peng Chen , Xiao Chen , Kang-yi Ren , Zheng-rong Chen , Zhe-min Zhou , Enmei Liu , Hong Tang","doi":"10.1016/j.jinf.2025.106642","DOIUrl":"10.1016/j.jinf.2025.106642","url":null,"abstract":"<div><div><em>Mycoplasma pneumoniae</em> (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with <em>M. pneumoniae</em>. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were <em>M. pneumoniae</em> mono-infected at hospitalization, and showed an expansion of both effector and memory CD8<sup>+</sup> T cells, with exhausted KLRG1<sup>hi</sup> CD8<sup>+</sup> T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM<sup>+</sup> plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8<sup>+</sup> T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated <em>M. pneumoniae</em> colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106642"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106649
David Crawford-Jones, Maisy Charlett, Louise Downs, Katie Jeffery
{"title":"Real-world utility of antigen-based testing (LumiraDX) for SARS-CoV-2 and influenza A/B in an acute hospital emergency care setting: a useful triage tool","authors":"David Crawford-Jones, Maisy Charlett, Louise Downs, Katie Jeffery","doi":"10.1016/j.jinf.2025.106649","DOIUrl":"10.1016/j.jinf.2025.106649","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106649"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106639
Yanan Li , Wenya Feng , Yunhua Yao , Lingyun Guo , Yuchuan Li , Huan Liu , Chengsong Zhao , Gang Liu
Objective
We aimed to investigate the temporal trends in the clinical and molecular epidemiology of pediatric hand, foot, and mouth disease (HFMD) since its designation as a notifiable disease (2008).
Methods
We retrospectively analyzed the pediatric HFMD cases from a single-center database from 2008 to 2024 and performed a binary logistic regression model to identify risk factors for severe disease among laboratory-confirmed cases.
Results
114,420 HFMD cases were reported over 17 years, including 569 severe cases (0.50%, 569/114,420) and 27 deaths (4.75%, 27/569). Following a peak in 2010, annual case numbers stabilized at approximately 10,000 from 2016, declined markedly after vaccine introduction, and dropped further during the COVID-19 pandemic, with a rebound in 2023. Before 2016, Coxsackievirus A16 (CV-A16) (30.66%) and Enterovirus 71 (EV-A71) (23.15%) were the predominant serotypes; subsequently, Coxsackievirus A6 (CV-A6) gradually emerged as the dominant circulating strain. A gradual increase in the age of affected children was observed, with a notable rise in cases among those aged ≥5 years during the post-pandemic period. Multivariable analysis revealed younger age, EV-A71 infection, and rural residence as independent risk factors for severe HFMD.
Conclusions
The evolving epidemiology of pediatric HFMD and the rising age of susceptibility highlight the need for continuous surveillance and early warning to guide prevention and strengthen public health response.
{"title":"Temporal trends in clinical and molecular epidemiology of pediatric hand, foot, and mouth disease, 2008-2024: Insights from 17 years of surveillance","authors":"Yanan Li , Wenya Feng , Yunhua Yao , Lingyun Guo , Yuchuan Li , Huan Liu , Chengsong Zhao , Gang Liu","doi":"10.1016/j.jinf.2025.106639","DOIUrl":"10.1016/j.jinf.2025.106639","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to investigate the temporal trends in the clinical and molecular epidemiology of pediatric hand, foot, and mouth disease (HFMD) since its designation as a notifiable disease (2008).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the pediatric HFMD cases from a single-center database from 2008 to 2024 and performed a binary logistic regression model to identify risk factors for severe disease among laboratory-confirmed cases.</div></div><div><h3>Results</h3><div>114,420 HFMD cases were reported over 17 years, including 569 severe cases (0.50%, 569/114,420) and 27 deaths (4.75%, 27/569). Following a peak in 2010, annual case numbers stabilized at approximately 10,000 from 2016, declined markedly after vaccine introduction, and dropped further during the COVID-19 pandemic, with a rebound in 2023. Before 2016, Coxsackievirus A16 (CV-A16) (30.66%) and Enterovirus 71 (EV-A71) (23.15%) were the predominant serotypes; subsequently, Coxsackievirus A6 (CV-A6) gradually emerged as the dominant circulating strain. A gradual increase in the age of affected children was observed, with a notable rise in cases among those aged ≥5 years during the post-pandemic period. Multivariable analysis revealed younger age, EV-A71 infection, and rural residence as independent risk factors for severe HFMD.</div></div><div><h3>Conclusions</h3><div>The evolving epidemiology of pediatric HFMD and the rising age of susceptibility highlight the need for continuous surveillance and early warning to guide prevention and strengthen public health response.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106639"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106632
Gijs Teunis , Timothy J. Dallman , Magdalena Zając , Magdalena Skarżyńska , Liljana Petrovska , Angela Pista , Leonor Silveira , Lurdes Clemente , Amandine Thépault , Laetitia Bonifait , Annaëlle Kerouanton , Marianne Chemaly , Julio Alvarez , Robert Söderlund , Eva Møller Nielsen , Marie Chattaway , Kaye Burgess , William Byrne , Aldert L. Zomer , Maaike van den Beld , Lapo Mughini-Gras
Non-typhoidal Salmonella is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic characterisation of Salmonella isolates from humans and animals has become a routine public health surveillance tool in many countries. In this study, the relative contributions of several potential sources of human infection of the five frequently reported Salmonella serovars were estimated using machine-learning methods based on a large, cross-sectional collection of genomes from human cases, and animal and environmental sources, across ten European countries. To define the population structure, core-genome Multilocus Sequence Typing was performed. A supervised machine-learning approach was applied for source attribution in the form of a Random Forest classifier. The source and country attribution models achieved moderate accuracy (F1=0.6–0.9), which is lower than in previous studies using machine-learning on Whole Genome Sequencing data. However, attributions of human clinical isolates to different sources were generally in line with previous findings for these five serovars. While the lack of clonality in some sources hindered their prediction, it is also likely that certain sources (e.g., pets) do not serve as major contributors to human infection. Therefore, in most cases attributing these sources to the livestock species they are typically associated with, is likely appropriate. Country attributions showed that substantial human cases are attributable to countries other than their own, indicating geographical interrelatedness of sources. This highlights the value of internationally harmonised Salmonella-control policies in the food production chain.
{"title":"Attributable sources of the five most prevalent non-typhoidal Salmonella serovars across ten European countries","authors":"Gijs Teunis , Timothy J. Dallman , Magdalena Zając , Magdalena Skarżyńska , Liljana Petrovska , Angela Pista , Leonor Silveira , Lurdes Clemente , Amandine Thépault , Laetitia Bonifait , Annaëlle Kerouanton , Marianne Chemaly , Julio Alvarez , Robert Söderlund , Eva Møller Nielsen , Marie Chattaway , Kaye Burgess , William Byrne , Aldert L. Zomer , Maaike van den Beld , Lapo Mughini-Gras","doi":"10.1016/j.jinf.2025.106632","DOIUrl":"10.1016/j.jinf.2025.106632","url":null,"abstract":"<div><div>Non-typhoidal <em>Salmonella</em> is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic characterisation of <em>Salmonella</em> isolates from humans and animals has become a routine public health surveillance tool in many countries. In this study, the relative contributions of several potential sources of human infection of the five frequently reported <em>Salmonella</em> serovars were estimated using machine-learning methods based on a large, cross-sectional collection of genomes from human cases, and animal and environmental sources, across ten European countries. To define the population structure, core-genome Multilocus Sequence Typing was performed. A supervised machine-learning approach was applied for source attribution in the form of a Random Forest classifier. The source and country attribution models achieved moderate accuracy (F1=0.6–0.9), which is lower than in previous studies using machine-learning on Whole Genome Sequencing data. However, attributions of human clinical isolates to different sources were generally in line with previous findings for these five serovars. While the lack of clonality in some sources hindered their prediction, it is also likely that certain sources (e.g., pets) do not serve as major contributors to human infection. Therefore, in most cases attributing these sources to the livestock species they are typically associated with, is likely appropriate. Country attributions showed that substantial human cases are attributable to countries other than their own, indicating geographical interrelatedness of sources. This highlights the value of internationally harmonised <em>Salmonella</em>-control policies in the food production chain.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106632"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106650
Lifang Yu , Mengwei Niu , Zhuofan Dong , Xue Dong , Yao Han , Jing An , Tao Jiang , Yuehong Chen , Ye Feng , Yansong Sun , Hao Li
Objectives
Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatment options for HAdV-55 are limited, with no specific antiviral drugs available. The CRISPR-Cas system, capable of precisely targeting viral genomes, has emerged as a novel approach for antiviral therapy. This study aimed to leverage targeted DNA cleavage activity of the CRISPR-Cas12a system to develop a therapeutic strategy for effectively inhibiting HAdV-55 replication.
Methods
We developed a rapid and efficient screening platform for identifying antiviral targets by integrating CRISPR-Cas12a fluorescence detection technology with bioinformatics analysis. Using this platform, we systematically screened 194 candidate targets against HAdV-55.
Results
The E1B-crRNA6-Cas12a system was identified, demonstrating a highly potent antiviral activity with 99.17% inhibitory efficiency and a selectivity index (SI) of 2482.80. This target significantly outperformed the clinical broad-spectrum anti-adenovirus drug cidofovir in both inhibitory efficacy and duration.
Conclusions
This study not only holds promise for providing safe and highly effective antiviral candidate targets for HAdV-55 therapy but also, through the construction of an interdisciplinary technical platform, is expected to enhance the translational potential of CRISPR antiviral technology for preclinical applications.
{"title":"High-efficiency inhibition of human adenovirus type 55 replication by CRISPR-Cas12a","authors":"Lifang Yu , Mengwei Niu , Zhuofan Dong , Xue Dong , Yao Han , Jing An , Tao Jiang , Yuehong Chen , Ye Feng , Yansong Sun , Hao Li","doi":"10.1016/j.jinf.2025.106650","DOIUrl":"10.1016/j.jinf.2025.106650","url":null,"abstract":"<div><h3>Objectives</h3><div>Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatment options for HAdV-55 are limited, with no specific antiviral drugs available. The CRISPR-Cas system, capable of precisely targeting viral genomes, has emerged as a novel approach for antiviral therapy. This study aimed to leverage targeted DNA cleavage activity of the CRISPR-Cas12a system to develop a therapeutic strategy for effectively inhibiting HAdV-55 replication.</div></div><div><h3>Methods</h3><div>We developed a rapid and efficient screening platform for identifying antiviral targets by integrating CRISPR-Cas12a fluorescence detection technology with bioinformatics analysis. Using this platform, we systematically screened 194 candidate targets against HAdV-55.</div></div><div><h3>Results</h3><div>The E1B-crRNA6-Cas12a system was identified, demonstrating a highly potent antiviral activity with 99.17% inhibitory efficiency and a selectivity index (SI) of 2482.80. This target significantly outperformed the clinical broad-spectrum anti-adenovirus drug cidofovir in both inhibitory efficacy and duration.</div></div><div><h3>Conclusions</h3><div>This study not only holds promise for providing safe and highly effective antiviral candidate targets for HAdV-55 therapy but also, through the construction of an interdisciplinary technical platform, is expected to enhance the translational potential of CRISPR antiviral technology for preclinical applications.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106650"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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