Pub Date : 2025-10-11DOI: 10.1016/j.virusres.2025.199641
Jingwei Hu , Min Liu , Binbin Qin , Bin Shen , Yingjun Huang , Jiayan Zhu , Qi Zheng , Xingdong Zheng , Jingyi Cai , Ying Xie , Yajun Song
Background
d-dimer, a fibrin degradation product and established marker of thrombosis, has been strongly associated with disease severity and poor prognosis in COVID-19. However, its role in immune modulation remains underexplored.
Methods
In this study, we enrolled 356 participants from Shanghai, including patients with mild and severe COVID-19 and SARS-CoV-2-negative controls. Clinical data were collected to assess correlations between d-dimer and immune-related markers. Public transcriptomic datasets, single-cell RNA sequencing (scRNA-seq), and in vitro stimulation of THP-1 cells with clinically relevant d-dimer concentrations were used to investigate d-dimer–associated immune responses.
Results
d-dimer levels were significantly elevated in severe COVID-19 patients and positively correlated with IL-6 and troponin I, while negatively associated with glomerular filtration rate. Integrated transcriptomic and protein interaction analyses identified IL-6 as a central hub in immune-related gene networks. scRNA-seq revealed tissue- and cell-specific IL-6 expression, predominantly in monocytes and T cells. In vitrod-dimer stimulation did not induce IL-6 expression in THP-1 cells but upregulated chemokines (e.g., CXCL5, CXCL6), and enriched key inflammatory pathways, including IL-17 and PI3K-Akt signaling.
Conclusion
These findings suggest that d-dimer may modulate the immune microenvironment by influencing chemokine-mediated cell recruitment, contributing to immune dysregulation in severe COVID-19. d-dimer functions not only as a clinical biomarker but also as a potential driver of thromboinflammatory responses.
{"title":"D-dimer drives immune dysregulation in COVID-19 via chemokine modulation and inflammatory signaling","authors":"Jingwei Hu , Min Liu , Binbin Qin , Bin Shen , Yingjun Huang , Jiayan Zhu , Qi Zheng , Xingdong Zheng , Jingyi Cai , Ying Xie , Yajun Song","doi":"10.1016/j.virusres.2025.199641","DOIUrl":"10.1016/j.virusres.2025.199641","url":null,"abstract":"<div><h3>Background</h3><div><span>d</span>-dimer, a fibrin degradation product and established marker of thrombosis, has been strongly associated with disease severity and poor prognosis in COVID-19. However, its role in immune modulation remains underexplored.</div></div><div><h3>Methods</h3><div>In this study, we enrolled 356 participants from Shanghai, including patients with mild and severe COVID-19 and SARS-CoV-2-negative controls. Clinical data were collected to assess correlations between <span>d</span>-dimer and immune-related markers. Public transcriptomic datasets, single-cell RNA sequencing (scRNA-seq), and <em>in vitro</em> stimulation of THP-1 cells with clinically relevant <span>d</span>-dimer concentrations were used to investigate <span>d</span>-dimer–associated immune responses.</div></div><div><h3>Results</h3><div><span>d</span>-dimer levels were significantly elevated in severe COVID-19 patients and positively correlated with IL-6 and troponin I, while negatively associated with glomerular filtration rate. Integrated transcriptomic and protein interaction analyses identified IL-6 as a central hub in immune-related gene networks. scRNA-seq revealed tissue- and cell-specific IL-6 expression, predominantly in monocytes and T cells. <em>In vitro</em> <span>d</span>-dimer stimulation did not induce IL-6 expression in THP-1 cells but upregulated chemokines (e.g., CXCL5, CXCL6), and enriched key inflammatory pathways, including IL-17 and PI3K-Akt signaling.</div></div><div><h3>Conclusion</h3><div>These findings suggest that <span>d</span>-dimer may modulate the immune microenvironment by influencing chemokine-mediated cell recruitment, contributing to immune dysregulation in severe COVID-19. <span>d</span>-dimer functions not only as a clinical biomarker but also as a potential driver of thromboinflammatory responses.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199641"},"PeriodicalIF":2.7,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1016/j.virusres.2025.199640
Dennis Rahenbrock, Mark Varrelmann
Plants are constantly challenged by viral pathogens that can limit growth and reduce yield. A key component of the plant innate immunity is RNA silencing, in which viral double-stranded RNA (dsRNA) intermediates are recognised and processed into virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs direct the degradation of viral genomes, thereby restricting infection. Sugar beet (Beta vulgaris subsp. vulgaris) is a crop of major economic importance, where the virus yellows (VY) complex represents a serious threat to production. Here, we profiled and compared vsiRNAs generated during infection of the natural host plant B. vulgaris and the experimental host plant Nicotiana benthamiana with three taxonomically distinct viruses: beet yellows virus (BYV, Closterovirus), beet mild yellowing virus (BMYV, Polerovirus), and beet mosaic virus (BtMV, Potyvirus). High-throughput sequencing of small RNAs revealed characteristic size distributions and strand biases that differed among viruses and host species. Comparative analysis highlighted no host plant-specific pattern of vsiRNA accumulation. This comparative approach provides a detailed view of vsiRNA processing and offers novel insights that are not apparent from coverage profiles alone. Distinct vsiRNA hotspots were detected for each viral genome, and these hotspots did not differ between host plants, pinpointing potential target regions for RNA interference-based control approaches. The identification of such regions provides a basis for the design of synthetic dsRNAs that can be applied exogenously as protective sprays, an emerging, non-transgenic strategy to mitigate VY infections, while advancing understanding of vsiRNA biogenesis in sugar beet and N. benthamiana in general.
{"title":"Comparative small RNA profiles of beet mosaic virus (BtMV), beet mild yellowing virus (BMYV) and beet yellows virus (BYV) infected Nicotiana benthamiana and Beta vulgaris","authors":"Dennis Rahenbrock, Mark Varrelmann","doi":"10.1016/j.virusres.2025.199640","DOIUrl":"10.1016/j.virusres.2025.199640","url":null,"abstract":"<div><div>Plants are constantly challenged by viral pathogens that can limit growth and reduce yield. A key component of the plant innate immunity is RNA silencing, in which viral double-stranded RNA (dsRNA) intermediates are recognised and processed into virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs direct the degradation of viral genomes, thereby restricting infection. Sugar beet (<em>Beta vulgaris</em> subsp. <em>vulgaris</em>) is a crop of major economic importance, where the virus yellows (VY) complex represents a serious threat to production. Here, we profiled and compared vsiRNAs generated during infection of the natural host plant <em>B. vulgaris</em> and the experimental host plant <em>Nicotiana benthamiana</em> with three taxonomically distinct viruses: beet yellows virus (BYV, <em>Closterovirus</em>), beet mild yellowing virus (BMYV, <em>Polerovirus</em>), and beet mosaic virus (BtMV, <em>Potyvirus</em>). High-throughput sequencing of small RNAs revealed characteristic size distributions and strand biases that differed among viruses and host species. Comparative analysis highlighted no host plant-specific pattern of vsiRNA accumulation. This comparative approach provides a detailed view of vsiRNA processing and offers novel insights that are not apparent from coverage profiles alone. Distinct vsiRNA hotspots were detected for each viral genome, and these hotspots did not differ between host plants, pinpointing potential target regions for RNA interference-based control approaches. The identification of such regions provides a basis for the design of synthetic dsRNAs that can be applied exogenously as protective sprays, an emerging, non-transgenic strategy to mitigate VY infections, while advancing understanding of vsiRNA biogenesis in sugar beet and <em>N. benthamiana</em> in general.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199640"},"PeriodicalIF":2.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-09DOI: 10.1016/j.virusres.2025.199638
Yijun Liu , Ge Jiang , Jie Cheng , Xiaotong Wang , Xianping Fan , Hailong Wu , Hui Shen
Vibrio parahaemolyticus causes mass mortality in global penaeid shrimp aquaculture worldwide, with lethality exceeding 90 %, threatening global food security and economic sustainability. As alternatives to antibiotics, bacteriophages and their lytic enzymes offer target specificity, minimal resistance development, and high bactericidal efficiency. In this study, ten phages were isolated from Litopenaeus vannamei aquaculture ponds and adjacent estuarine areas using Vp499 as the host, which were isolated by our lab. Among these, phage SHY-Vp8 exhibited the highest titer against the host Vp499.Its optimal multiplicity of infection (MOI) was determined to be 1. Notably, SHY-Vp8 demonstrated a superior lytic capacity, with a high burst size (96 PFU/cell) and a short latent period (30 min), representing an 18–41 % improvement in lytic efficiency over previously reported Vibrio phages. Furthermore, it exhibited exceptional environmental resilience, tolerating temperatures up to 60 °C and a broad pH range (3–12), surpassing the stability thresholds of most known vibriophages. Whole-genome sequencing indicated a double-stranded DNA genome of 58,525 bp with 46.38 % GC content. Bioinformatic annotation identified 85 predicted genes, of which 31 encoded functionally characterized proteins. No tRNA or virulence genes were detected, demonstrating potential for therapeutic applications in aquaculture. Transmission electron microscopy confirmed an icosahedral capsid and a long non-contractile tail, classifying SHY-Vp8 within the Siphoviridae family. Notably, the gp59 gene was predicted to encode an endolysin. The gene was amplified cloned and expressed. The lytic activity of Lys59 exhibited a concentration-dependent increase, with peak activity observed at 50 μg/mL. Lys59 alone was capable of lysing Vp499 without the aid of EDTA; however, pretreatment with EDTA significantly enhanced its lytic efficiency. Results indicate that both SHY-Vp8 and Lys59 exhibit promising potential for controlling V. parahaemolyticus infections in L. vannamei, offering a novel and sustainable strategy for disease management in aquaculture—particularly in pond water treatment and seafood safety enhancement. These excellent in vitro activities and characteristics provide a solid foundation for further development of in vivo infection models and eco-friendly biocontrol agents.
{"title":"Isolation, genomic analysis and biocontrol potential of bacteriophage SHY-Vp8 and its endolysin against Vibrio parahaemolyticus in shrimp aquaculture","authors":"Yijun Liu , Ge Jiang , Jie Cheng , Xiaotong Wang , Xianping Fan , Hailong Wu , Hui Shen","doi":"10.1016/j.virusres.2025.199638","DOIUrl":"10.1016/j.virusres.2025.199638","url":null,"abstract":"<div><div><em>Vibrio parahaemolyticus</em> causes mass mortality in global penaeid shrimp aquaculture worldwide, with lethality exceeding 90 %, threatening global food security and economic sustainability. As alternatives to antibiotics, bacteriophages and their lytic enzymes offer target specificity, minimal resistance development, and high bactericidal efficiency. In this study, ten phages were isolated from <em>Litopenaeus vannamei</em> aquaculture ponds and adjacent estuarine areas using Vp499 as the host, which were isolated by our lab. Among these, phage SHY-Vp8 exhibited the highest titer against the host Vp499.Its optimal multiplicity of infection (MOI) was determined to be 1. Notably, SHY-Vp8 demonstrated a superior lytic capacity, with a high burst size (96 PFU/cell) and a short latent period (30 min), representing an 18–41 % improvement in lytic efficiency over previously reported <em>Vibrio</em> phages. Furthermore, it exhibited exceptional environmental resilience, tolerating temperatures up to 60 °C and a broad pH range (3–12), surpassing the stability thresholds of most known vibriophages. Whole-genome sequencing indicated a double-stranded DNA genome of 58,525 bp with 46.38 % GC content. Bioinformatic annotation identified 85 predicted genes, of which 31 encoded functionally characterized proteins. No tRNA or virulence genes were detected, demonstrating potential for therapeutic applications in aquaculture. Transmission electron microscopy confirmed an icosahedral capsid and a long non-contractile tail, classifying SHY-Vp8 within the Siphoviridae family. Notably, the gp59 gene was predicted to encode an endolysin. The gene was amplified cloned and expressed. The lytic activity of Lys59 exhibited a concentration-dependent increase, with peak activity observed at 50 μg/mL. Lys59 alone was capable of lysing Vp499 without the aid of EDTA; however, pretreatment with EDTA significantly enhanced its lytic efficiency. Results indicate that both SHY-Vp8 and Lys59 exhibit promising potential for controlling <em>V. parahaemolyticus</em> infections in L. <em>vannamei</em>, offering a novel and sustainable strategy for disease management in aquaculture—particularly in pond water treatment and seafood safety enhancement. These excellent in vitro activities and characteristics provide a solid foundation for further development of in vivo infection models and eco-friendly biocontrol agents.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199638"},"PeriodicalIF":2.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/j.virusres.2025.199639
Siyu Zhu , Qi Zhong , Yang Zhang , Lizhen Hou , Hongzhi Ma , Ling Feng , Xixi Shen , Jiaming Chen , Yurong He , Jingwen Lyu , Tiantian Wang , Rui Zhao , Jingfeng Li , Jugao Fang , Shizhi He
This study aims to evaluate the safety and preliminary efficacy of VT1093, an oncolytic recombinant herpes simplex virus type 1 (HSV-1) engineered to express a PD-1 monoclonal antibody, for the treatment of recurrent head and neck cancer. This open-label, single-arm, dose-escalation Phase I clinical trial was an exploratory dose-escalation study, in which the dose is progressively increased in enrolled patients until either the maximum tolerated dose (MTD) or dose-limiting toxicity (DLT) is identified. Seven patients with recurrent head and neck cancer were recruited at Beijing Tongren Hospital. Patients received either a single or multiple intratumoral injections of VT1093. For the single-dose group, patients were monitored for 28 days after treatment. For the multiple-dose group, three treatments were administered biweekly, with a 28-day follow-up after the final injection. Treatment efficacy and adverse events were monitored and recorded throughout the study. Of the seven patients enrolled, five were eligible for efficacy evaluation. Two patients did not return for follow-up evaluation after treatment and were classified as treatment ineffective. Four patients achieved stable disease (SD), while one had progressive disease (PD), resulting in a disease control rate (DCR) of 57.1 % (4/7). The most common treatment-related adverse events were mild to moderate fever and fatigue (Grade 1–2), with no Grade 3 or higher events. A promising immune profile was found in response to the oncolytic virus injection combined with PD-1 antibody. The treatment was generally well tolerated, and no DLTs were observed. VT1093 shows promising efficacy in controlling disease progression in recurrent head and neck cancer, with a favorable safety profile and low toxicity. These results support further clinical development of VT1093 as a novel therapeutic approach for this patient population.
{"title":"Phase I clinical trial of a recombinant oncolytic virus injection combined with PD-1 antibody-based gene therapy for recurrent head and neck cancer in China: An open-label study","authors":"Siyu Zhu , Qi Zhong , Yang Zhang , Lizhen Hou , Hongzhi Ma , Ling Feng , Xixi Shen , Jiaming Chen , Yurong He , Jingwen Lyu , Tiantian Wang , Rui Zhao , Jingfeng Li , Jugao Fang , Shizhi He","doi":"10.1016/j.virusres.2025.199639","DOIUrl":"10.1016/j.virusres.2025.199639","url":null,"abstract":"<div><div>This study aims to evaluate the safety and preliminary efficacy of VT1093, an oncolytic recombinant herpes simplex virus type 1 (HSV-1) engineered to express a PD-1 monoclonal antibody, for the treatment of recurrent head and neck cancer. This open-label, single-arm, dose-escalation Phase I clinical trial was an exploratory dose-escalation study, in which the dose is progressively increased in enrolled patients until either the maximum tolerated dose (MTD) or dose-limiting toxicity (DLT) is identified. Seven patients with recurrent head and neck cancer were recruited at Beijing Tongren Hospital. Patients received either a single or multiple intratumoral injections of VT1093. For the single-dose group, patients were monitored for 28 days after treatment. For the multiple-dose group, three treatments were administered biweekly, with a 28-day follow-up after the final injection. Treatment efficacy and adverse events were monitored and recorded throughout the study. Of the seven patients enrolled, five were eligible for efficacy evaluation. Two patients did not return for follow-up evaluation after treatment and were classified as treatment ineffective. Four patients achieved stable disease (SD), while one had progressive disease (PD), resulting in a disease control rate (DCR) of 57.1 % (4/7). The most common treatment-related adverse events were mild to moderate fever and fatigue (Grade 1–2), with no Grade 3 or higher events. A promising immune profile was found in response to the oncolytic virus injection combined with PD-1 antibody. The treatment was generally well tolerated, and no DLTs were observed. VT1093 shows promising efficacy in controlling disease progression in recurrent head and neck cancer, with a favorable safety profile and low toxicity. These results support further clinical development of VT1093 as a novel therapeutic approach for this patient population.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199639"},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-03DOI: 10.1016/j.virusres.2025.199637
Liaqat Ali , Nida Kanwal , Iffat Saleem , Haidar Ali , Deeba Amraiz , Madiha Akram , Imran Shahid , Jing Yang
Dengue virus (DENV) remains a global health threat, with Pakistan experiencing recurrent outbreaks, yet non-structural genes (NS1, NS2A, NS5) critical for viral replication and pathogenesis remain understudied in local strains. In this study, 150 NS1-positive serum samples (2022–2024) were analyzed via nested PCR, Sanger sequencing, and phylogenetic tools (MEGA11), revealing DENV-2 as the dominant serotype (85 % of samples), with NS5 showing 97 % homology to Indian/Swat strains, while NS1 and NS2A exhibited sequence variation in functional domains. In silico modeling and docking studies identified RK-0404,678 as a strong binder to NS5 (−6.4 kcal/mol) and Galidesivir to NS5 (−7.2 kcal/mol), suggesting their potential as antiviral candidates. These findings highlight DENV-2 dominance in Pakistan and identify conserved regions in NS5 as promising drug targets, though further experimental validation is warranted.
{"title":"Molecular and structural insights into dengue virus non-structural proteins from pakistani clinical isolates for the identification of novel antiviral targets","authors":"Liaqat Ali , Nida Kanwal , Iffat Saleem , Haidar Ali , Deeba Amraiz , Madiha Akram , Imran Shahid , Jing Yang","doi":"10.1016/j.virusres.2025.199637","DOIUrl":"10.1016/j.virusres.2025.199637","url":null,"abstract":"<div><div>Dengue virus (DENV) remains a global health threat, with Pakistan experiencing recurrent outbreaks, yet non-structural genes (NS1, NS2A, NS5) critical for viral replication and pathogenesis remain understudied in local strains. In this study, 150 NS1-positive serum samples (2022–2024) were analyzed via nested PCR, Sanger sequencing, and phylogenetic tools (MEGA11), revealing DENV-2 as the dominant serotype (85 % of samples), with NS5 showing 97 % homology to Indian/Swat strains, while NS1 and NS2A exhibited sequence variation in functional domains. <em>In silico</em> modeling and docking studies identified RK-0404,678 as a strong binder to NS5 (−6.4 kcal/mol) and Galidesivir to NS5 (−7.2 kcal/mol), suggesting their potential as antiviral candidates. These findings highlight DENV-2 dominance in Pakistan and identify conserved regions in NS5 as promising drug targets, though further experimental validation is warranted.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199637"},"PeriodicalIF":2.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.virusres.2025.199635
Weiwei Li , Wei Jiao , Fang Li , Jie Hao
<div><h3>Objective</h3><div>To observe the effect of interleukin-17A (IL-17A) on serum anti-mitochondrial endosomal ADP/ATP carrier autoantibody (anti-ANT antibody) levels and cytokines in viral myocarditis (VMC) mice.</div></div><div><h3>Methods</h3><div>Male wild-type (WT) and IL-17A knockout (IL-17A<sup>−/−</sup>) BALB/c mice were intraperitoneally injected with coxsackievirus B3 (CVB3) to establish a VMC model (VMC-WT and VMC-IL-17A<sup>−/−</sup>), while WT BALB/c mice were injected with PBS intraperitoneally to establish a normal control group (WT group). After 14 days, myocardial tissues were taken to calculate heart mass, and paraffin sections were prepared and stained with HE staining to observe the pathological changes and calculate the pathological score of myocardial tissues. Flow cytometry was used to detect the level of CD4<sup>+</sup> T lymphocytes in peripheral blood, ELISA was used to determine the level of anti-ANT antibody, IL-17 and IL-23 in serum, and Western blotting was used to detect the expression level of IL-17 and IL-23 proteins in myocardial tissue.</div></div><div><h3>Results</h3><div>VMC mice were successfully constructed. Mice in the WT group showed no abnormal activity; Mice in the VMC-WT group gradually showed behaviors such as huddling, shrugging, trembling, and poor response from the third day of injection; Mice in the VMC-IL-17A<sup>−/−</sup> group showed the above symptoms to a lesser extent. In the VMC-WT group, the HM and pathological score were 5.62 ± 0.27 g/kg and 3.12 ± 0.45 score. The HM and pathologic score in the VMC-IL-17A<sup>−/−</sup> group were lower than those in the VMC-WT group. The pathological examination of WT mice showed no inflammatory cell infiltration and patchy necrosis. The rats in VMC-WT group showed extensive inflammatory cell infiltration and large sheet necrosis of cardiomyocytes under microscope. Compared with the VMC-WT group, the VMC-IL-17A<sup>−/−</sup> group showed focal myocardial necrosis and significantly reduced inflammatory cell infiltration 14 days after CVB3 infection. At the same time, the percentage of CD4<sup>+</sup>T was remarkably lower in the VMC-WT mice compared with the WT mice. The percentage of CD4<sup>+</sup>T was higher in the VMC-IL-17A<sup>−/−</sup> group (27.54 ± 3.62) than in the VMC-WT group (16.97 ± 2.18). In addition, anti-ANT antibody (1.48 ± 0.31 μg/L), IL-17 (33.47 ± 4.26 pg/mL) and IL-23 (32.42 ± 4.31 pg/mL) levels were significantly lower in serum of VMC-IL-17A<sup>−/−</sup> mice than in the VMC-WT mice. At the protein level, the expression of IL-17 and IL-23 showed consistent results.</div></div><div><h3>Conclusion</h3><div>Serum anti-ANT antibody, IL-17, and IL-23 levels were significantly elevated in VMC mice. Although the ELISA results suggest IL-17A is involved in the production of anti-ANT antibody in VMC mice, the possibility of cross-reactivity cannot be completely ruled out; therefore, the results should be interpreted with caution. The kn
{"title":"Effect of interleukin-17A on anti-ANT antibodies as well as cytokines in viral myocarditis mice","authors":"Weiwei Li , Wei Jiao , Fang Li , Jie Hao","doi":"10.1016/j.virusres.2025.199635","DOIUrl":"10.1016/j.virusres.2025.199635","url":null,"abstract":"<div><h3>Objective</h3><div>To observe the effect of interleukin-17A (IL-17A) on serum anti-mitochondrial endosomal ADP/ATP carrier autoantibody (anti-ANT antibody) levels and cytokines in viral myocarditis (VMC) mice.</div></div><div><h3>Methods</h3><div>Male wild-type (WT) and IL-17A knockout (IL-17A<sup>−/−</sup>) BALB/c mice were intraperitoneally injected with coxsackievirus B3 (CVB3) to establish a VMC model (VMC-WT and VMC-IL-17A<sup>−/−</sup>), while WT BALB/c mice were injected with PBS intraperitoneally to establish a normal control group (WT group). After 14 days, myocardial tissues were taken to calculate heart mass, and paraffin sections were prepared and stained with HE staining to observe the pathological changes and calculate the pathological score of myocardial tissues. Flow cytometry was used to detect the level of CD4<sup>+</sup> T lymphocytes in peripheral blood, ELISA was used to determine the level of anti-ANT antibody, IL-17 and IL-23 in serum, and Western blotting was used to detect the expression level of IL-17 and IL-23 proteins in myocardial tissue.</div></div><div><h3>Results</h3><div>VMC mice were successfully constructed. Mice in the WT group showed no abnormal activity; Mice in the VMC-WT group gradually showed behaviors such as huddling, shrugging, trembling, and poor response from the third day of injection; Mice in the VMC-IL-17A<sup>−/−</sup> group showed the above symptoms to a lesser extent. In the VMC-WT group, the HM and pathological score were 5.62 ± 0.27 g/kg and 3.12 ± 0.45 score. The HM and pathologic score in the VMC-IL-17A<sup>−/−</sup> group were lower than those in the VMC-WT group. The pathological examination of WT mice showed no inflammatory cell infiltration and patchy necrosis. The rats in VMC-WT group showed extensive inflammatory cell infiltration and large sheet necrosis of cardiomyocytes under microscope. Compared with the VMC-WT group, the VMC-IL-17A<sup>−/−</sup> group showed focal myocardial necrosis and significantly reduced inflammatory cell infiltration 14 days after CVB3 infection. At the same time, the percentage of CD4<sup>+</sup>T was remarkably lower in the VMC-WT mice compared with the WT mice. The percentage of CD4<sup>+</sup>T was higher in the VMC-IL-17A<sup>−/−</sup> group (27.54 ± 3.62) than in the VMC-WT group (16.97 ± 2.18). In addition, anti-ANT antibody (1.48 ± 0.31 μg/L), IL-17 (33.47 ± 4.26 pg/mL) and IL-23 (32.42 ± 4.31 pg/mL) levels were significantly lower in serum of VMC-IL-17A<sup>−/−</sup> mice than in the VMC-WT mice. At the protein level, the expression of IL-17 and IL-23 showed consistent results.</div></div><div><h3>Conclusion</h3><div>Serum anti-ANT antibody, IL-17, and IL-23 levels were significantly elevated in VMC mice. Although the ELISA results suggest IL-17A is involved in the production of anti-ANT antibody in VMC mice, the possibility of cross-reactivity cannot be completely ruled out; therefore, the results should be interpreted with caution. The kn","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199635"},"PeriodicalIF":2.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.virusres.2025.199636
Yasmine Chelbi , Manel Hamdoun , Hamza Cherni , Hinda Triki , Melika Ben Ahmed , Olfa Bahri
Chronic infection with the hepatitis B virus (HBV) remains a major public health issue. Its progression depends on several factors, including immunogenetic factors. The aim of this study was to investigate the association between interleukin 10 gene (IL10) polymorphism and the progression of this infection. This retrospective case-control study involved 156 chronic HBV carriers (CHBV-C) and 174 healthy HBV-negative controls (HBsAg-). The analysis of IL10 promoter polymorphism was carried out using the TaqMan allele discrimination technique at two single nucleotide polymorphisms (SNPs), -592A>C (rs1800872) and -1082A>G (rs1800896), of the IL10 promoter. IL10 levels were measured using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) for all patients chronically infected by HBV who had not yet received treatment. Chronic HBV infection (CBI) was present in 32% (n = 43) of cases, 37% (n = 51) had active chronic hepatitis (ACH), and 31% had complicated hepatitis. The analysis of allele polymorphism identified six genotypes: AA (14%), AC (43%), and CC (43%) for SNP-592A>C, and AA (41%), AG (45%) and GG (14%) for SNP-1082A>G. The only genotype that was substantially more common in CHBV-C patients was -1082/GG (OR=1.9; CI95%=[1,3.62]; p = 0.046). When compared to controls, the IL10 level was significantly higher in CBI patients (3.27 vs. 2.56 pg/ml;p = 0.002). Significantly higher IL10 levels were also linked to the genotypes -1082 GG (6.02 pg/ml;p = 0.04) and -592CC (3.73 pg/ml;p = 0.039). With the -592 AA genotype, this level was noticeably lower (1.35 pg/ml;p = 0.014). These findings support the hypothesis that the development of chronicity in HBV infection is linked to elevated IL10 levels and the -1082 GG genotype in the gene's promoter.
{"title":"Impact of IL10 polymorphism in chronic progression of hepatitis B virus infection","authors":"Yasmine Chelbi , Manel Hamdoun , Hamza Cherni , Hinda Triki , Melika Ben Ahmed , Olfa Bahri","doi":"10.1016/j.virusres.2025.199636","DOIUrl":"10.1016/j.virusres.2025.199636","url":null,"abstract":"<div><div>Chronic infection with the hepatitis B virus (HBV) remains a major public health issue. Its progression depends on several factors, including immunogenetic factors. The aim of this study was to investigate the association between interleukin 10 gene (<em>IL10</em>) polymorphism and the progression of this infection. This retrospective case-control study involved 156 chronic HBV carriers (CHBV-C) and 174 healthy HBV-negative controls (HBsAg-). The analysis of <em>IL10</em> promoter polymorphism was carried out using the TaqMan allele discrimination technique at two single nucleotide polymorphisms (SNPs), -592A><em>C</em> (rs1800872) and -1082A><em>G</em> (rs1800896), of the <em>IL10</em> promoter. IL10 levels were measured using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) for all patients chronically infected by HBV who had not yet received treatment. Chronic HBV infection (CBI) was present in 32% (<em>n</em> = 43) of cases, 37% (<em>n</em> = 51) had active chronic hepatitis (ACH), and 31% had complicated hepatitis. The analysis of allele polymorphism identified six genotypes: AA (14%), AC (43%), and CC (43%) for SNP-592A><em>C</em>, and AA (41%), AG (45%) and GG (14%) for SNP-1082A><em>G</em>. The only genotype that was substantially more common in CHBV-C patients was -1082/GG (OR=1.9; CI95%=[1,3.62]; <em>p</em> = 0.046). When compared to controls, the IL10 level was significantly higher in CBI patients (3.27 vs. 2.56 pg/ml;<em>p</em> = 0.002). Significantly higher IL10 levels were also linked to the genotypes -1082 GG (6.02 pg/ml;<em>p</em> = 0.04) and -592CC (3.73 pg/ml;<em>p</em> = 0.039). With the -592 AA genotype, this level was noticeably lower (1.35 pg/ml;<em>p</em> = 0.014). These findings support the hypothesis that the development of chronicity in HBV infection is linked to elevated IL10 levels and the -1082 GG genotype in the gene's promoter.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199636"},"PeriodicalIF":2.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-21DOI: 10.1016/j.virusres.2025.199634
Chloé Chavoix , Pascale Massin , François-Xavier Briand , Katell Louboutin , Rachel Busson , Florent Souchaud , Gautier Richard , Claire Martenot , Aurélie Le Roux , Edouard Hirchaud , Yannick Blanchard , Sophie Le Bouquin-Leneveu , Axelle Scoizec , Céline Deblanc , Séverine Hervé , Audrey Schmitz , Eric Niqueux , Gaëlle Simon , Ronan Le Goffic , Béatrice Grasland
Influenza A viruses (IAVs) circulate among animals and humans and can cross species barriers to adapt to new hosts. In France, since 2020, a new genotype named H1avN2#E has predominated in pig farms. In parallel, this virus was detected in 19 breeding turkey flocks and in a human case, indicating interspecies transmission. The objectives of this study were (i) to analyze viral sequences detected in turkeys between April 2020 and January 2023 and compare them with swine sequences to identify potential markers of adaptation and (ii) to characterize three representative viruses in vitro and in ovo on MDCK, MLE15 and A549 cells, as well as on embryonated chicken eggs. Results suggest that following initial swine-to-turkey spillovers, the virus circulated between turkey farms. Phylogenetic analyses and host origin guided the selection of three viruses: a reference swine virus (A), a turkey strain closely related to swine viruses (B) and a virus apparently circulating in turkeys (C). Three molecular markers may contribute to turkey adaptation: the E233K, under positive selection pressure, or E236K mutations in the 220-loop of the receptor-binding site of HA protein and two NA substitutions, T401N in antigenic site 2d and S416N. Replication kinetics showed that at low MOI (0.001), virus C produced more infectious particles on MDCK and A549 cells, whereas at high MOI (0.1), virus B produced more. In ovo, infectious particles were generated for viruses A and B but not efficiently for virus C, in contrast to mammalian cells where production was higher.
{"title":"Identification of H1N2 influenza viruses in turkeys after spillover from swine and in vitro characterization","authors":"Chloé Chavoix , Pascale Massin , François-Xavier Briand , Katell Louboutin , Rachel Busson , Florent Souchaud , Gautier Richard , Claire Martenot , Aurélie Le Roux , Edouard Hirchaud , Yannick Blanchard , Sophie Le Bouquin-Leneveu , Axelle Scoizec , Céline Deblanc , Séverine Hervé , Audrey Schmitz , Eric Niqueux , Gaëlle Simon , Ronan Le Goffic , Béatrice Grasland","doi":"10.1016/j.virusres.2025.199634","DOIUrl":"10.1016/j.virusres.2025.199634","url":null,"abstract":"<div><div>Influenza A viruses (IAVs) circulate among animals and humans and can cross species barriers to adapt to new hosts. In France, since 2020, a new genotype named H1<sub>av</sub>N2#E has predominated in pig farms. In parallel, this virus was detected in 19 breeding turkey flocks and in a human case, indicating interspecies transmission. The objectives of this study were (i) to analyze viral sequences detected in turkeys between April 2020 and January 2023 and compare them with swine sequences to identify potential markers of adaptation and (ii) to characterize three representative viruses <em>in vitro</em> and <em>in ovo</em> on MDCK, MLE15 and A549 cells, as well as on embryonated chicken eggs. Results suggest that following initial swine-to-turkey spillovers, the virus circulated between turkey farms. Phylogenetic analyses and host origin guided the selection of three viruses: a reference swine virus (A), a turkey strain closely related to swine viruses (B) and a virus apparently circulating in turkeys (C). Three molecular markers may contribute to turkey adaptation: the E233K, under positive selection pressure, or E236K mutations in the 220-loop of the receptor-binding site of HA protein and two NA substitutions, T401N in antigenic site 2d and S416N. Replication kinetics showed that at low MOI (0.001), virus C produced more infectious particles on MDCK and A549 cells, whereas at high MOI (0.1), virus B produced more. <em>In ovo</em>, infectious particles were generated for viruses A and B but not efficiently for virus C, in contrast to mammalian cells where production was higher.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199634"},"PeriodicalIF":2.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.virusres.2025.199633
Zoltán Vokó , Gergő Túri , Beatrix Oroszi , Éva Belicza , Tamás Kováts , Veronika Müller , János Réthelyi , Attila Szijártó , Tamás Masszi , István Takács , János Gál , Zsolt Göböl , Attila Szabó , Csaba Varga , Dávid Becker , Béla Merkely
COVID-19 vaccines reduce hospitalization risk, but data on severe outcomes are limited. We analyzed the impact of COVID-19 vaccination on severe outcomes in hospitalized patients in Hungary during the pre-Omicron era, addressing a regional knowledge gap. This retrospective study included hospitalized patients with PCR-confirmed COVID-19 (March 2020 – December 2021) who were categorized as unvaccinated, primary immunized, or booster-vaccinated. Outcomes included oxygen therapy, ventilation types, ECMO, and death, with the most severe outcome as the primary outcome and individual outcomes as secondary measures. Polytomous logistic regression calculated relative risk ratios for the primary outcome and COVID-19 vaccination status, while logistic regression estimated odds ratios for individual outcomes. During the study, 7575 patients were hospitalized with PCR-confirmed COVID-19: 6420 (84.8 %) were unvaccinated, 1016 (13.4 %) received a primary vaccination series, and 139 (1.8 %) had received a booster dose. COVID-19 vaccination reduced the risk of both invasive ventilation and in-hospital death as the most severe outcome by 50 % within 12 months (relative risk ratio [RRR]: 0.52, 95 % CI: 0.30–0.89; 0.50, 95 % CI: 0.41–0.61). Booster doses within six months decreased the risk of in-hospital death to a similar extent (RRR 0.46, 95 % CI: 0.30–0.72). Primary and booster vaccination reduced the risk of progression to severe outcomes in hospitalized COVID-19 patients.
{"title":"Association between COVID-19 vaccination and progression to severe outcomes in hospitalized COVID-19 patients in Hungary during the pre-Omicron era of the COVID-19 pandemic","authors":"Zoltán Vokó , Gergő Túri , Beatrix Oroszi , Éva Belicza , Tamás Kováts , Veronika Müller , János Réthelyi , Attila Szijártó , Tamás Masszi , István Takács , János Gál , Zsolt Göböl , Attila Szabó , Csaba Varga , Dávid Becker , Béla Merkely","doi":"10.1016/j.virusres.2025.199633","DOIUrl":"10.1016/j.virusres.2025.199633","url":null,"abstract":"<div><div>COVID-19 vaccines reduce hospitalization risk, but data on severe outcomes are limited. We analyzed the impact of COVID-19 vaccination on severe outcomes in hospitalized patients in Hungary during the pre-Omicron era, addressing a regional knowledge gap. This retrospective study included hospitalized patients with PCR-confirmed COVID-19 (March 2020 – December 2021) who were categorized as unvaccinated, primary immunized, or booster-vaccinated. Outcomes included oxygen therapy, ventilation types, ECMO, and death, with the most severe outcome as the primary outcome and individual outcomes as secondary measures. Polytomous logistic regression calculated relative risk ratios for the primary outcome and COVID-19 vaccination status, while logistic regression estimated odds ratios for individual outcomes. During the study, 7575 patients were hospitalized with PCR-confirmed COVID-19: 6420 (84.8 %) were unvaccinated, 1016 (13.4 %) received a primary vaccination series, and 139 (1.8 %) had received a booster dose. COVID-19 vaccination reduced the risk of both invasive ventilation and in-hospital death as the most severe outcome by 50 % within 12 months (relative risk ratio [RRR]: 0.52, 95 % CI: 0.30–0.89; 0.50, 95 % CI: 0.41–0.61). Booster doses within six months decreased the risk of in-hospital death to a similar extent (RRR 0.46, 95 % CI: 0.30–0.72). Primary and booster vaccination reduced the risk of progression to severe outcomes in hospitalized COVID-19 patients.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199633"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11DOI: 10.1016/j.virusres.2025.199630
Jehad Zuhair Tayyeb , Maria Karolaynne da Silva , Aamal A. Al-Mutairi , Hanan M. Alharbi , Alaa A. Khojah , Imren Bayıl , Abdullah Yahya Abdullah Alzahrani , Zsolt Tóth , Jonas Ivan Nobre Oliveira , Magdi E.A. Zaki
Zika virus (ZIKV) infection remains a global health threat with no approved antivirals or vaccines to date, creating an urgent need for therapeutics targeting ZIKV. The viral envelope (E) protein is critical for host cell entry and represents a validated target for antiviral intervention. Here, we aimed to identify natural flavonoid compounds capable of inhibiting the ZIKV E protein using a dual-phase in silico screening strategy. First, we performed density functional theory (DFT) calculations to optimize the structures of nine candidate flavonoids and obtain quantum chemical descriptors (electronic properties); we also evaluated their drug-likeness and ADMET profiles. Second, we conducted molecular docking of these optimized flavonoids to the E protein, followed by hybrid quantum mechanics/molecular mechanics (QM/MM) refinement and 100 ns molecular dynamics (MD) simulations with principal component analysis (PCA) and MM-PBSA binding free energy calculations to assess binding interactions and complex stability. Docking identified quercetin, pinocembrin, and naringenin as the top binders, with binding energies of –8.3, –8.1, and –8.0 kcal/mol, respectively. These lead flavonoids also exhibited favorable pharmacokinetic properties, including high predicted gastrointestinal absorption, efficient clearance, and minimal toxicity risk (no carcinogenic or organ-specific alerts). Notably, pinocembrin’s complex demonstrated the greatest stability throughout a 100 ns MD simulation, maintaining a tightly bound conformation. In conclusion, quercetin, pinocembrin, and naringenin emerge as promising ZIKV E protein inhibitors with robust target engagement and favorable drug-like profiles. Their significant translational potential as antiviral candidates warrants further in vitro and in vivo studies to confirm efficacy and safety.
{"title":"Evaluation of Potential Inhibitors of Zika Virus Envelope Protein Through Molecular Docking and Molecular Dynamics Simulation","authors":"Jehad Zuhair Tayyeb , Maria Karolaynne da Silva , Aamal A. Al-Mutairi , Hanan M. Alharbi , Alaa A. Khojah , Imren Bayıl , Abdullah Yahya Abdullah Alzahrani , Zsolt Tóth , Jonas Ivan Nobre Oliveira , Magdi E.A. Zaki","doi":"10.1016/j.virusres.2025.199630","DOIUrl":"10.1016/j.virusres.2025.199630","url":null,"abstract":"<div><div>Zika virus (ZIKV) infection remains a global health threat with no approved antivirals or vaccines to date, creating an urgent need for therapeutics targeting ZIKV. The viral envelope (E) protein is critical for host cell entry and represents a validated target for antiviral intervention. Here, we aimed to identify natural flavonoid compounds capable of inhibiting the ZIKV E protein using a dual-phase <em>in silico</em> screening strategy. First, we performed density functional theory (DFT) calculations to optimize the structures of nine candidate flavonoids and obtain quantum chemical descriptors (electronic properties); we also evaluated their drug-likeness and ADMET profiles. Second, we conducted molecular docking of these optimized flavonoids to the E protein, followed by hybrid quantum mechanics/molecular mechanics (QM/MM) refinement and 100 ns molecular dynamics (MD) simulations with principal component analysis (PCA) and MM-PBSA binding free energy calculations to assess binding interactions and complex stability. Docking identified quercetin, pinocembrin, and naringenin as the top binders, with binding energies of –8.3, –8.1, and –8.0 kcal/mol, respectively. These lead flavonoids also exhibited favorable pharmacokinetic properties, including high predicted gastrointestinal absorption, efficient clearance, and minimal toxicity risk (no carcinogenic or organ-specific alerts). Notably, pinocembrin’s complex demonstrated the greatest stability throughout a 100 ns MD simulation, maintaining a tightly bound conformation. In conclusion, quercetin, pinocembrin, and naringenin emerge as promising ZIKV E protein inhibitors with robust target engagement and favorable drug-like profiles. Their significant translational potential as antiviral candidates warrants further <em>in vitro</em> and <em>in vivo</em> studies to confirm efficacy and safety.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199630"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}