Pub Date : 2025-11-01DOI: 10.1016/j.virusres.2025.199654
Ming Wu , Jun Liu , Hui Li , Rui Yang
The life cycle of human papillomavirus (HPV) is intricate, and a lack of appropriate in vitro models for natural HPV infection has led to a dearth of effective treatments for infection and related tumors. The HPV life cycle is strictly dependent on the differentiation of epithelial cells. Therefore, in our previous study, we used conditional reprogramming(CR) technology to establish human vaginal intraepithelial neoplasia cell infected with HPV18 naturally (VIN18) and verified that HPV18 completes its viral life cycle in these cells. This article refers to it as VIN18. In this study, we utilize VIN18 to establish a 3D differentiation model that facilitates a time gradient of infection within raft-like organotypic cultures.Our findings clarify previous understanding of the interaction between HPV18 and the host during the viral physiological cycle. We observed that under undifferentiated conditions, ATM-CHK2 is not essential for the genomic stability of HPV18. However, the differentiation environment primarily activates HPV18 amplification via ATM/CHK2 signaling. CHK2 exerts negative feedback regulation on the activity of upstream ATM. Moreover, upregulation of p53 and p21 leads to a reduction in cyclin D1. Consequently, increased HPV18 E7 expression induces the re-entry of VIN18 cells into S phase, resulting in elevated expression of cyclin A2 and cyclin B1, which causes the cell cycle arrest in S phase/G2 phase, thereby supporting viral genome amplification. This study provides a valuable new model for HPV biology research and offers insights into the regulation of the HPV life cycle through the differentiation process.
{"title":"Negative feedback regulation of CHK2 in VIN18 raft cultures naturally infected with HPV18","authors":"Ming Wu , Jun Liu , Hui Li , Rui Yang","doi":"10.1016/j.virusres.2025.199654","DOIUrl":"10.1016/j.virusres.2025.199654","url":null,"abstract":"<div><div>The life cycle of human papillomavirus (HPV) is intricate, and a lack of appropriate in vitro models for natural HPV infection has led to a dearth of effective treatments for infection and related tumors. The HPV life cycle is strictly dependent on the differentiation of epithelial cells. Therefore, in our previous study, we used conditional reprogramming(CR) technology to establish human vaginal intraepithelial neoplasia cell infected with HPV18 naturally (VIN18) and verified that HPV18 completes its viral life cycle in these cells. This article refers to it as VIN18. In this study, we utilize VIN18 to establish a 3D differentiation model that facilitates a time gradient of infection within raft-like organotypic cultures.Our findings clarify previous understanding of the interaction between HPV18 and the host during the viral physiological cycle. We observed that under undifferentiated conditions, ATM-CHK2 is not essential for the genomic stability of HPV18. However, the differentiation environment primarily activates HPV18 amplification via ATM/CHK2 signaling. CHK2 exerts negative feedback regulation on the activity of upstream ATM. Moreover, upregulation of p53 and p21 leads to a reduction in cyclin D1. Consequently, increased HPV18 E7 expression induces the re-entry of VIN18 cells into S phase, resulting in elevated expression of cyclin A2 and cyclin B1, which causes the cell cycle arrest in S phase/G2 phase, thereby supporting viral genome amplification. This study provides a valuable new model for HPV biology research and offers insights into the regulation of the HPV life cycle through the differentiation process.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199654"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439220","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}
Human papillomavirus 16 (HPV16) is a major carcinogenic HPV type responsible for both cervical cancer (CC) and oropharyngeal cancer (OPC). HPV16 E6 polymorphisms vary by geographic region and are correlated with disease progression. Here, we sought to investigate HPV16 E6 variation in Japanese patients and evaluate its clinical relevance. We enrolled 379 patients with CC and OPC, and subjected 100 CC and 71 OPC samples with HPV16 DNA to E6 sequence analysis. The E6 sequence was partially deleted in 13 (13 %) CCs and 16 (23 %) OPCs. Patients with OPC harboring defective E6 had significantly worse overall survival than those with intact E6. This was observed in univariate analysis but not in multivariate analysis when adjusted for viral load. These findings indicate that low viral load is an independent prognostic factor in patients with OPC, and that E6 deletion is associated with low viral load. By contrast, prognostic differences were not observed in patients with CC. In summary, we report a newly identified gene deletion within the HPV16 E6 region associated with low viral load. These findings will facilitate further studies on the clinical and oncological significance of E6 deletion in patients with HPV16-related malignancies.
{"title":"Detection of partial deletions of the human papillomavirus 16 E6 gene in a subset of oropharyngeal and cervical cancers","authors":"Yumiko Hashida , Shuichi Matsumoto , Nagamasa Maeda , Masanori Teshima , Masanori Daibata","doi":"10.1016/j.virusres.2025.199648","DOIUrl":"10.1016/j.virusres.2025.199648","url":null,"abstract":"<div><div>Human papillomavirus 16 (HPV16) is a major carcinogenic HPV type responsible for both cervical cancer (CC) and oropharyngeal cancer (OPC). HPV16 <em>E6</em> polymorphisms vary by geographic region and are correlated with disease progression. Here, we sought to investigate HPV16 <em>E6</em> variation in Japanese patients and evaluate its clinical relevance. We enrolled 379 patients with CC and OPC, and subjected 100 CC and 71 OPC samples with HPV16 DNA to <em>E6</em> sequence analysis. The <em>E6</em> sequence was partially deleted in 13 (13 %) CCs and 16 (23 %) OPCs. Patients with OPC harboring defective <em>E6</em> had significantly worse overall survival than those with intact <em>E6</em>. This was observed in univariate analysis but not in multivariate analysis when adjusted for viral load. These findings indicate that low viral load is an independent prognostic factor in patients with OPC, and that <em>E6</em> deletion is associated with low viral load. By contrast, prognostic differences were not observed in patients with CC. In summary, we report a newly identified gene deletion within the HPV16 <em>E6</em> region associated with low viral load. These findings will facilitate further studies on the clinical and oncological significance of <em>E6</em> deletion in patients with HPV16-related malignancies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199648"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370389","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199646
Jing Zhou , Qigao Chen , Bolin Cheng , Lianzhong Li , Yihao Yang , Yongping Lin
The clinical effects of pediatric human adenovirus (HAdV) 7 infection are more severe than those caused by HAdV-3. This increased pathogenesis is likely associated with a higher viremia, i.e., a higher presence of HAdV-7 in blood, but the mechanisms that explain this are poorly understood. Herein, we tested the polarization of entry and release for both HAdV-7 or HAdV-3 in epithelial and endothelial cells, and evaluated the effect of these viruses on cellular junctions of epithelial cells, measuring transepithelial electrical resistance and paracellular flux. We show that epithelial cells are infected by both viruses via either basolateral or apical sides, but are released apically. In contrast, in endothelials cells, both entry and release can occur from either side. The replication capacity was higher for HAdV-7 than for HAdV-3, and infection led to more severe epithelial barrier damage, compromising tight junction integrity. These effects may be related to the higher viremia observed previously in HAdV-7. The way in which HAdV-7 traverses epithelial and endothelial barriers to establish a new infection offers new perspectives to treat its pathogenicity.
{"title":"Higher viremia and pathogenesis of human adenovirus 7 is likely associated to enhanced disruption of junction integrity","authors":"Jing Zhou , Qigao Chen , Bolin Cheng , Lianzhong Li , Yihao Yang , Yongping Lin","doi":"10.1016/j.virusres.2025.199646","DOIUrl":"10.1016/j.virusres.2025.199646","url":null,"abstract":"<div><div>The clinical effects of pediatric human adenovirus (HAdV) 7 infection are more severe than those caused by HAdV-3. This increased pathogenesis is likely associated with a higher viremia, i.e., a higher presence of HAdV-7 in blood, but the mechanisms that explain this are poorly understood. Herein, we tested the polarization of entry and release for both HAdV-7 or HAdV-3 in epithelial and endothelial cells, and evaluated the effect of these viruses on cellular junctions of epithelial cells, measuring transepithelial electrical resistance and paracellular flux. We show that epithelial cells are infected by both viruses via either basolateral or apical sides, but are released apically. In contrast, in endothelials cells, both entry and release can occur from either side. The replication capacity was higher for HAdV-7 than for HAdV-3, and infection led to more severe epithelial barrier damage, compromising tight junction integrity. These effects may be related to the higher viremia observed previously in HAdV-7. The way in which HAdV-7 traverses epithelial and endothelial barriers to establish a new infection offers new perspectives to treat its pathogenicity.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199646"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356033","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199650
Xiaomin Zhang , Jing Wu , Yalan Huang , Chunli Wu , Yue Li , Renli Zhang , Xiaohe Li , Bo Peng , Fan Yang
<div><h3>Background</h3><div>An exhaustive analysis of the immunological and pathogenic features of the first locally acquired case of severe fever with thrombocytopenia syndrome (SFTS) in Shenzhen was conducted.</div></div><div><h3>Methods</h3><div>Serum samples were dynamically collected from one patient presenting with fever and thrombocytopenia, as well as from his close contacts. The presence of Dabie bandavirus (DBV) RNA was detected using fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR), while specific IgM and IgG antibodies were identified via enzyme-linked immunosorbent assay (ELISA). The viral L (large), M (medium), and S (small) segments were sequentially amplified by PCR and then sequenced using Sanger sequencing. We performed amino acid comparisons with published DBV strain sequences to identify mutation sites and assess their potential functional implications. Subsequently, molecular genotyping was conducted, and segment reassortment and recombination analyses were performed for each viral segment.</div></div><div><h3>Results</h3><div>A 52-year-old man presented with a history of fever, mild cough, dizziness, and fatigue. Serum samples from the patient tested positive for Dabie bandavirus (DBV) nucleic acid five days after disease onset, while blood samples taken 12 days after onset were positive for DBV-specific IgM and negative for both nucleic acid and DBV-specific IgG. The L, M, and S segments of the virus strain named SZ-202,101 showed the highest sequence homology with the DBV strain HB2012–197 from Hubei Province; the similarities were 99.50 %, 99.49 %, and 99.60 %, respectively. When compared to the reference DBV strain HB29, SZ-202,101 exhibited amino acid mutations at 16, 24, and 6 sites in the L, M, and S segments, respectively. The mutations in the L segment were predominantly located in the Linker, Core Lobe, vRBL, Fingers, Fingermode, Thumb Ring, and CBD domains. For the M segment, mutations were concentrated in the A, B, β, C, IM, I, III, TM, and Linker domains. The S segment mutations were primarily found in the N-lobe and C-terminal domains. Genetic evolution analysis revealed that the L and S segments of the SZ-202,101 strain and the HB2012–197 strain were classified under the B genotype, while the M segment was associated with the C genotype; consequently, the genotype of SZ-202,101 was designated as BCB. The virus did not exhibit any signs of recombination. Regarding epidemiological investigation, given that the patient and his associate had no record of international travel or contact with known cases, this instance was classified as an autochthonous case. This marks the first local case of SFTS in Shenzhen since 2017 and the first identification of DBV genotype reassortment in the region.</div></div><div><h3>Conclusion</h3><div>The Local case of SFTS in Shenzhen was attributed to a genetically reassorted DBVidentified as the BCB reassortment genotype. The potential influence of
{"title":"Characterization of a local case of severe fever with thrombocytopenia syndrome in Shenzhen, China: Clinical and immunological insights","authors":"Xiaomin Zhang , Jing Wu , Yalan Huang , Chunli Wu , Yue Li , Renli Zhang , Xiaohe Li , Bo Peng , Fan Yang","doi":"10.1016/j.virusres.2025.199650","DOIUrl":"10.1016/j.virusres.2025.199650","url":null,"abstract":"<div><h3>Background</h3><div>An exhaustive analysis of the immunological and pathogenic features of the first locally acquired case of severe fever with thrombocytopenia syndrome (SFTS) in Shenzhen was conducted.</div></div><div><h3>Methods</h3><div>Serum samples were dynamically collected from one patient presenting with fever and thrombocytopenia, as well as from his close contacts. The presence of Dabie bandavirus (DBV) RNA was detected using fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR), while specific IgM and IgG antibodies were identified via enzyme-linked immunosorbent assay (ELISA). The viral L (large), M (medium), and S (small) segments were sequentially amplified by PCR and then sequenced using Sanger sequencing. We performed amino acid comparisons with published DBV strain sequences to identify mutation sites and assess their potential functional implications. Subsequently, molecular genotyping was conducted, and segment reassortment and recombination analyses were performed for each viral segment.</div></div><div><h3>Results</h3><div>A 52-year-old man presented with a history of fever, mild cough, dizziness, and fatigue. Serum samples from the patient tested positive for Dabie bandavirus (DBV) nucleic acid five days after disease onset, while blood samples taken 12 days after onset were positive for DBV-specific IgM and negative for both nucleic acid and DBV-specific IgG. The L, M, and S segments of the virus strain named SZ-202,101 showed the highest sequence homology with the DBV strain HB2012–197 from Hubei Province; the similarities were 99.50 %, 99.49 %, and 99.60 %, respectively. When compared to the reference DBV strain HB29, SZ-202,101 exhibited amino acid mutations at 16, 24, and 6 sites in the L, M, and S segments, respectively. The mutations in the L segment were predominantly located in the Linker, Core Lobe, vRBL, Fingers, Fingermode, Thumb Ring, and CBD domains. For the M segment, mutations were concentrated in the A, B, β, C, IM, I, III, TM, and Linker domains. The S segment mutations were primarily found in the N-lobe and C-terminal domains. Genetic evolution analysis revealed that the L and S segments of the SZ-202,101 strain and the HB2012–197 strain were classified under the B genotype, while the M segment was associated with the C genotype; consequently, the genotype of SZ-202,101 was designated as BCB. The virus did not exhibit any signs of recombination. Regarding epidemiological investigation, given that the patient and his associate had no record of international travel or contact with known cases, this instance was classified as an autochthonous case. This marks the first local case of SFTS in Shenzhen since 2017 and the first identification of DBV genotype reassortment in the region.</div></div><div><h3>Conclusion</h3><div>The Local case of SFTS in Shenzhen was attributed to a genetically reassorted DBVidentified as the BCB reassortment genotype. The potential influence of","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199650"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466502","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199657
Liwei Zhang , Yingfei Li , Xuehui Zhang , Jing Zhao , Guozhong Zhang , Ye Zhao
Infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), is a contagious respiratory disease of chickens that poses a serious threat to the poultry industry worldwide. In this study, four monoclonal antibodies (mAbs) targeting the heptad repeat 2 (HR2) region of the spike protein S2 subunit were generated through mouse immunization, hybridoma cell fusion, and clonal purification. Western blot and indirect immunofluorescence assays confirmed that all four mAbs specifically recognized IBV. Epitope identification revealed two novel linear B-cell epitopes: 1040KWWND1044, recognized by mAbs 6A6 and 6E2; and 1046KHELPDF1052, recognized by mAbs 6A1 and 6A9, which are conserved among different IBV lineages. Furthermore, both epitopes are exposed on the surface of the spike protein, suggesting their potential as immunologically relevant targets. This study contributes to further elucidating the structure and function of the IBV S2 subunit and provide assistance for the development of IBV diagnostic technology.
{"title":"Two novel conserved linear B-cell epitopes identified in the S2 subunit of the infectious bronchitis virus spike protein","authors":"Liwei Zhang , Yingfei Li , Xuehui Zhang , Jing Zhao , Guozhong Zhang , Ye Zhao","doi":"10.1016/j.virusres.2025.199657","DOIUrl":"10.1016/j.virusres.2025.199657","url":null,"abstract":"<div><div>Infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), is a contagious respiratory disease of chickens that poses a serious threat to the poultry industry worldwide. In this study, four monoclonal antibodies (mAbs) targeting the heptad repeat 2 (HR2) region of the spike protein S2 subunit were generated through mouse immunization, hybridoma cell fusion, and clonal purification. Western blot and indirect immunofluorescence assays confirmed that all four mAbs specifically recognized IBV. Epitope identification revealed two novel linear B-cell epitopes: <sup>1040</sup>KWWND<sup>1044</sup>, recognized by mAbs 6A6 and 6E2; and <sup>1046</sup>KHELPDF<sup>1052</sup>, recognized by mAbs 6A1 and 6A9, which are conserved among different IBV lineages. Furthermore, both epitopes are exposed on the surface of the spike protein, suggesting their potential as immunologically relevant targets. This study contributes to further elucidating the structure and function of the IBV S2 subunit and provide assistance for the development of IBV diagnostic technology.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199657"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452968","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199653
Valentina Andreoli , Sofia Lopez , Santiago Germán Delgado , Sandra Elizabeth Pérez , Susana Beatriz Pereyra , Erika Analía Gonzalez Altamiranda , Florencia Romeo , Stefano Grolli , Andrea Elizabeth Verna
Reproductive viral diseases caused by Bovine alphaherpesvirus 1.1 (BoAHV-1.1), Bovine gam-maherpesvirus 4 (BoGHV-4), and Bovine viral diarrhoea virus (BVDV) impose a substantial economic burden on the cattle industry, primarily through infertility, abortion, and impaired reproductive performance. Owing to the limited efficacy of current antiviral strategies, this study evaluated the in vitro effects of platelet-rich plasma (PRP), at concentrations of 5 % and 10 %, on the replication kinetics of these viruses in Madin-Darby bovine kidney (MDBK) cells and primary bovine endometrial stromal cells (BESc). PRP modulated viral replication in a virus-, cell type-, and dose-related manner. In BoAHV-1.1-infected MDBK cells, 10 % PRP reduced extracellular titres but increases intracellular accumulation, suggesting interference with viral egress. In BESc, both intra- and extracellular titres decreased, consistent with a broader antiviral effect. For BoGHV-4 and BVDV, PRP induced variable and time-dependent responses across cell types. These results demonstrate that PRP can influence bovine viral replication dynamics in vitro and support further investigations into its mechanistic basis and in vivo therapeutic potential.
{"title":"Modulatory effects of platelet-rich plasma on viral kinetics of BoAHV-1.1, BoGHV-4, and BVDV in bovine cell cultures: A proof-of-concept study","authors":"Valentina Andreoli , Sofia Lopez , Santiago Germán Delgado , Sandra Elizabeth Pérez , Susana Beatriz Pereyra , Erika Analía Gonzalez Altamiranda , Florencia Romeo , Stefano Grolli , Andrea Elizabeth Verna","doi":"10.1016/j.virusres.2025.199653","DOIUrl":"10.1016/j.virusres.2025.199653","url":null,"abstract":"<div><div>Reproductive viral diseases caused by Bovine alphaherpesvirus 1.1 (BoAHV-1.1), Bovine gam-maherpesvirus 4 (BoGHV-4), and Bovine viral diarrhoea virus (BVDV) impose a substantial economic burden on the cattle industry, primarily through infertility, abortion, and impaired reproductive performance. Owing to the limited efficacy of current antiviral strategies, this study evaluated the <em>in vitro</em> effects of platelet-rich plasma (PRP), at concentrations of 5 % and 10 %, on the replication kinetics of these viruses in Madin-Darby bovine kidney (MDBK) cells and primary bovine endometrial stromal cells (BESc). PRP modulated viral replication in a virus-, cell type-, and dose-related manner. In BoAHV-1.1-infected MDBK cells, 10 % PRP reduced extracellular titres but increases intracellular accumulation, suggesting interference with viral egress. In BESc, both intra- and extracellular titres decreased, consistent with a broader antiviral effect. For BoGHV-4 and BVDV, PRP induced variable and time-dependent responses across cell types. These results demonstrate that PRP can influence bovine viral replication dynamics <em>in vitro</em> and support further investigations into its mechanistic basis and <em>in vivo</em> therapeutic potential.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199653"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432140","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199649
Yan Qian , Zhichen Zhu , Jie Zhu , Liang Chen , Hong Du
Antibiotic-resistant bacteria pose a significant threat to human health worldwide. Phages, natural parasitic viruses of bacteria, have the capability to kill bacterial hosts, including those resistant to antibiotics. With traditional antimicrobials becoming increasingly ineffective and research into new antibiotics waning, bacteriophage therapies are gaining renewed attention. This review discusses recent progress and experiences with phage therapy in the treatment of pulmonary infections. Emerging phage therapy is effective in treating pulmonary infections, and no adverse effects have been observed in animal models and compassionate use cases in humans to date, which encompasses synergistic treatments that combine phages with antibiotics, the use of phage derivatives, the integration of phages with bioengineering, and the development of phage vaccines. Additionally, current limitations of phage therapy are introduced. Due to the lack of pharmacokinetic data in vivo, there is no unified standard for phage dosing regimen. However, in general, phage therapy has great potential in the treatment of pulmonary infections.
{"title":"Phage therapy: Innovative approaches for refractory pulmonary infections","authors":"Yan Qian , Zhichen Zhu , Jie Zhu , Liang Chen , Hong Du","doi":"10.1016/j.virusres.2025.199649","DOIUrl":"10.1016/j.virusres.2025.199649","url":null,"abstract":"<div><div>Antibiotic-resistant bacteria pose a significant threat to human health worldwide. Phages, natural parasitic viruses of bacteria, have the capability to kill bacterial hosts, including those resistant to antibiotics. With traditional antimicrobials becoming increasingly ineffective and research into new antibiotics waning, bacteriophage therapies are gaining renewed attention. This review discusses recent progress and experiences with phage therapy in the treatment of pulmonary infections. Emerging phage therapy is effective in treating pulmonary infections, and no adverse effects have been observed in animal models and compassionate use cases in humans to date, which encompasses synergistic treatments that combine phages with antibiotics, the use of phage derivatives, the integration of phages with bioengineering, and the development of phage vaccines. Additionally, current limitations of phage therapy are introduced. Due to the lack of pharmacokinetic data in <em>vivo</em>, there is no unified standard for phage dosing regimen. However, in general, phage therapy has great potential in the treatment of pulmonary infections.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199649"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417071","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199652
Rong Wen , Jiahao Tong , Shoude Liu , Chengbo Zheng , Jinshui Zheng , Donghai Peng , Ming Sun
Escherichia coli phage vB_EcoS_P78, a novel bacteriophage isolated from swine feces, exhibits typical siphovirus morphology with an isometric head and a non-contractile tail, forming clear plaques approximately 4 mm in diameter. It demonstrated a broad host range, lysing 75 % of tested ESBL-producing and MDR E. coli clinical isolates across multiple serogroups. The phage displayed strong stability, retaining activity at temperatures up to 50 °C and within a pH range of 3–10. Results from one-step growth assays showed a 20-minute latent period and that each infected cell produced a burst size of 220 PFU. Whole-genome sequencing revealed a 44,574 bp dsDNA genome containing 58 ORFs, with no antibiotic resistance, and virulence genes detected. Phylogenetic analysis based on intergenomic similarity and core protein phylogeny consistently supported its classification within the genus Dhillonvirus, showing 92.8 % similarity to Escherichia phage JL1. These results indicate that vB_EcoS_P78 represents a novel species of Dhillonvirus with potential therapeutic applications against multidrug-resistant E. coli.
{"title":"Isolation and characterization of a novel lytic bacteriophage vB_EcoS_P78 against multidrug-resistant Escherichia coli","authors":"Rong Wen , Jiahao Tong , Shoude Liu , Chengbo Zheng , Jinshui Zheng , Donghai Peng , Ming Sun","doi":"10.1016/j.virusres.2025.199652","DOIUrl":"10.1016/j.virusres.2025.199652","url":null,"abstract":"<div><div><em>Escherichia coli</em> phage vB_EcoS_P78, a novel bacteriophage isolated from swine feces, exhibits typical siphovirus morphology with an isometric head and a non-contractile tail, forming clear plaques approximately 4 mm in diameter. It demonstrated a broad host range, lysing 75 % of tested ESBL-producing and MDR <em>E. coli</em> clinical isolates across multiple serogroups. The phage displayed strong stability, retaining activity at temperatures up to 50 °C and within a pH range of 3–10. Results from one-step growth assays showed a 20-minute latent period and that each infected cell produced a burst size of 220 PFU. Whole-genome sequencing revealed a 44,574 bp dsDNA genome containing 58 ORFs, with no antibiotic resistance, and virulence genes detected. Phylogenetic analysis based on intergenomic similarity and core protein phylogeny consistently supported its classification within the genus <em>Dhillonvirus</em>, showing 92.8 % similarity to <em>Escherichia</em> phage JL1. These results indicate that vB_EcoS_P78 represents a novel species of <em>Dhillonvirus</em> with potential therapeutic applications against multidrug-resistant <em>E. coli</em>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199652"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422721","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199643
Raphael O. Adegbola, Dinusha C. Maheepala, Ursula K. Schuch, Judith K. Brown
The palo verde tree is native to the Sonoran Desert and consists of multiple species classified in the genus Parkinsonia, family, Fabaceae. Palo verde broom virus (PVBV), Fimoviridae, Emaravirus, is the suspect causal agent of witches’ broom disease of blue palo verde, P. florida. Here, PVBV was detected in four palo verde species and two hybrids by reverse transcription polymerase chain reaction (RT-PCR) amplification of a 679-base pair (bp) fragment of RNA3, which encodes the nucleocapsid gene (NP). The prevalence of witches’ broom symptoms among the different Parkinsonia species (n = 70), collected from naturally-occurring, nursery- or urban landscape trees was 54 %. Within-species PVBV infection spanned 50–100 % and 81 % across four species and two hybrids combined. The PVBV genome segments RNAs 1–5 were de novo and reference based-assembled from Illumina® RNAseq reads obtained from total RNA isolated from PVBV-positive trees. Pairwise nucleotide identity and amino acid identity for 29 field isolates and GenBank reference PVBV RNA1–5 segments/predicted proteins was 73–100 % and 68–100 %, respectively. Phylogenetic analysis of concatenated RNA1–5 segments resolved four sister clades with no basis in host range among the four palo verde species or hybrids. Five predicted recombinants were identified with breakpoints in either tfhe RNA1 or RNA5 genomic segment. Consistent recovery of PVBV full-length genomes from four Parkinsonia spp. and two hybrids indicated that additional Parkinsonia species and hybrids besides blue palo verde, the only previously reported host, harbored PVBV. Previous studies have linked emaravirus transmission with Eriophyidae mite vectors. Here, the palo verde mite Aculus cercidii Keifer (Eriophyidae) (1965) counts ranged from eight to >1000 per tree. Prolific or minimally-detectable colonization of PVBV-infected trees by A. cercidii, together with consistent detection of PVBV in symptomatic and asymptomatic trees implicate the palo verde mite as the vector of and PVBV as the causal agent of witches’ broom disease.
{"title":"Prevalence, host range, and characterization of multiple Palo verde broom emaravirus genomes and eriophyid mites from Parkinsonia spp. in Arizona","authors":"Raphael O. Adegbola, Dinusha C. Maheepala, Ursula K. Schuch, Judith K. Brown","doi":"10.1016/j.virusres.2025.199643","DOIUrl":"10.1016/j.virusres.2025.199643","url":null,"abstract":"<div><div>The palo verde tree is native to the Sonoran Desert and consists of multiple species classified in the genus <em>Parkinsonia</em>, family, Fabaceae. Palo verde broom virus (PVBV), <em>Fimoviridae, Emaravirus,</em> is the suspect causal agent of witches’ broom disease of blue palo verde, <em>P. florida</em>. Here, PVBV was detected in four palo verde species and two hybrids by reverse transcription polymerase chain reaction (RT-PCR) amplification of a 679-base pair (bp) fragment of RNA3, which encodes the nucleocapsid gene (NP). The prevalence of witches’ broom symptoms among the different <em>Parkinsonia</em> species (<em>n</em> = 70), collected from naturally-occurring, nursery- or urban landscape trees was 54 %. Within-species PVBV infection spanned 50–100 % and 81 % across four species and two hybrids combined. The PVBV genome segments RNAs 1–5 were <em>de novo</em> and reference based-assembled from Illumina® RNAseq reads obtained from total RNA isolated from PVBV-positive trees. Pairwise nucleotide identity and amino acid identity for 29 field isolates and GenBank reference PVBV RNA1–5 segments/predicted proteins was 73–100 % and 68–100 %, respectively. Phylogenetic analysis of concatenated RNA1–5 segments resolved four sister clades with no basis in host range among the four palo verde species or hybrids. Five predicted recombinants were identified with breakpoints in either tfhe RNA1 or RNA5 genomic segment. Consistent recovery of PVBV full-length genomes from four <em>Parkinsonia</em> spp. and two hybrids indicated that additional <em>Parkinsonia</em> species and hybrids besides blue palo verde, the only previously reported host, harbored PVBV. Previous studies have linked emaravirus transmission with <em>Eriophyidae</em> mite vectors. Here, the palo verde mite <em>Aculus cercidii</em> Keifer (<em>Eriophyidae</em>) (1965) counts ranged from eight to >1000 per tree. Prolific or minimally-detectable colonization of PVBV-infected trees by <em>A. cercidii</em>, together with consistent detection of PVBV in symptomatic and asymptomatic trees implicate the palo verde mite as the vector of and PVBV as the causal agent of witches’ broom disease.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199643"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318682","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 : 2025-11-01DOI: 10.1016/j.virusres.2025.199647
Huixin Li, Yaping Qin, Zongxi Han, Shengwang Liu
To adapt the infectious bronchitis virus (IBV) for cell culture, the tl/CH/LDT3/03 strain was subjected to serial passaging in chicken embryo fibroblasts (CEFs) and Vero cells, respectively. Cytopathic effects (CPEs) first became apparent at the 7th passage in CEFs and the 11th passage in Vero cells, respectively. The tl/CH/LDT3/03 strain achieved stable replication and adaptation after 20 passages in CEFs (CEA P20) and 25 passages in Vero cells (VEA P25). Analysis of the genomic sequences of the two adapted viruses identified amino acid substitutions, insertions, and deletions in some of the viral proteins. To evaluate the replication capacity of the cell-adapted viruses, 1-day-old SPF chicks were inoculated with either CEA P20 or VEA P25. Both CEA P20 and VEA P25 exhibited reduced replication capacity in chickens, as determined by viral titration in 11 selected tissues collected at 5 days post-inoculation (dpi). The pathogenicity of the two viruses was also decreased for 1-day-old chicks. Furthermore, VEA P25 elicited significantly reduced neutralizing antibody responses in infected birds, nearly 3-fold lower than that induced by CEA P20. To evaluate protective efficacy for chickens, in ovo vaccination of SPF eggs with either CEA P20 or VEA P25 was carried out. Both cell-adapted viruses provided complete protection against tl/CH/LDT3/03 challenge, therefore represent promising attenuated live vaccine candidates for in ovo vaccination. In conclusion, serial propagation of IBV tl/CH/LDT3/03 in CEFs and Vero cells resulted in successful viral adaptation, which was associated with decreased replication capacity and a consequent attenuation of virulence in chickens, showing the potential of live vaccine candidates against tl/CH/LDT3/03.
{"title":"Attenuation and altered replication of IBV strain tl/CH/LDT3/03 after serial passage in chicken embryo fibroblasts and Vero cells","authors":"Huixin Li, Yaping Qin, Zongxi Han, Shengwang Liu","doi":"10.1016/j.virusres.2025.199647","DOIUrl":"10.1016/j.virusres.2025.199647","url":null,"abstract":"<div><div>To adapt the infectious bronchitis virus (IBV) for cell culture, the tl/CH/LDT3/03 strain was subjected to serial passaging in chicken embryo fibroblasts (CEFs) and Vero cells, respectively. Cytopathic effects (CPEs) first became apparent at the 7th passage in CEFs and the 11th passage in Vero cells, respectively. The tl/CH/LDT3/03 strain achieved stable replication and adaptation after 20 passages in CEFs (CEA P20) and 25 passages in Vero cells (VEA P25). Analysis of the genomic sequences of the two adapted viruses identified amino acid substitutions, insertions, and deletions in some of the viral proteins. To evaluate the replication capacity of the cell-adapted viruses, 1-day-old SPF chicks were inoculated with either CEA P20 or VEA P25. Both CEA P20 and VEA P25 exhibited reduced replication capacity in chickens, as determined by viral titration in 11 selected tissues collected at 5 days post-inoculation (dpi). The pathogenicity of the two viruses was also decreased for 1-day-old chicks. Furthermore, VEA P25 elicited significantly reduced neutralizing antibody responses in infected birds, nearly 3-fold lower than that induced by CEA P20. To evaluate protective efficacy for chickens, <em>in ovo</em> vaccination of SPF eggs with either CEA P20 or VEA P25 was carried out. Both cell-adapted viruses provided complete protection against tl/CH/LDT3/03 challenge, therefore represent promising attenuated live vaccine candidates for <em>in ovo</em> vaccination. In conclusion, serial propagation of IBV tl/CH/LDT3/03 in CEFs and Vero cells resulted in successful viral adaptation, which was associated with decreased replication capacity and a consequent attenuation of virulence in chickens, showing the potential of live vaccine candidates against tl/CH/LDT3/03.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199647"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356028","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}
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