Pub Date : 2025-11-14DOI: 10.1016/j.virusres.2025.199664
Madeline I. Petrusic, Sarah K. McLean, Enzo A. Palombo
Numerous reports have revealed that the bacterium Vibrio parahaemolyticus is responsible for significant economic losses in aquaculture and poses a threat to public health. In search of a sustainable biocontrol agent against V. parahaemolyticus, two lytic and novel bacteriophages, VpP1 and VpP2, were characterised. Both phages exhibited broad host ranges, lysing 13/16 V. parahaemolyticus strains. Phages were imaged by transmission electron microscopy, and analysis revealed that both phages exhibit morphology consistent with members of the class Caudoviricetes. Both phages inhibited the growth of their respective host bacterium with a high multiplicity of infection. All treated cultures had a substantial reduction in viability compared to non-treated cultures. One-step growth curve analysis revealed a latent period of approximately 22 min for both phages. The burst sizes were calculated as 10.2 PFU/mL, and 7.3 PFU/mL for VpP1 and VpP2, respectively. Stability determination assays revealed both phages could withstand a broad salinity range (1 to 20 %), pH levels (3.0–10.0), temperatures (-20 to 60 °C) and sodium hydrochlorite levels (3 to 10 mg/mL). Phages VpP1 and VpP2 could withstand direct UV light for 4 and 5 min, respectively. Next-generations sequencing revealed that VpP1 (63,510 bp) and VpP2 (64,298 bp) did not contain known virulence, antibiotic-resistance or lysogenic genes, highlighting their capability to be used as biocontrol agents. Phylogenetic analysis based on the major head protein revealed that VpP1 and VpP2 were categorised into the newly described Mardecavirus genus. The results suggest VpP1 and VpP2 have several beneficial qualities for future use as biocontrol agents. Further study is still required to determine their efficiency within food applications.
{"title":"Characterisation of newly identified vibriophages and their potential application in the biocontrol of Vibrio parahaemolyticus to enhance safety in aquaculture","authors":"Madeline I. Petrusic, Sarah K. McLean, Enzo A. Palombo","doi":"10.1016/j.virusres.2025.199664","DOIUrl":"10.1016/j.virusres.2025.199664","url":null,"abstract":"<div><div>Numerous reports have revealed that the bacterium <em>Vibrio parahaemolyticus</em> is responsible for significant economic losses in aquaculture and poses a threat to public health. In search of a sustainable biocontrol agent against <em>V. parahaemolyticus</em>, two lytic and novel bacteriophages, VpP1 and VpP2, were characterised. Both phages exhibited broad host ranges, lysing 13/16 V<em>. parahaemolyticus</em> strains. Phages were imaged by transmission electron microscopy, and analysis revealed that both phages exhibit morphology consistent with members of the class <em>Caudoviricetes</em>. Both phages inhibited the growth of their respective host bacterium with a high multiplicity of infection. All treated cultures had a substantial reduction in viability compared to non-treated cultures. One-step growth curve analysis revealed a latent period of approximately 22 min for both phages. The burst sizes were calculated as 10.2 PFU/mL, and 7.3 PFU/mL for VpP1 and VpP2, respectively. Stability determination assays revealed both phages could withstand a broad salinity range (1 to 20 %), pH levels (3.0–10.0), temperatures (-20 to 60 °C) and sodium hydrochlorite levels (3 to 10 mg/mL). Phages VpP1 and VpP2 could withstand direct UV light for 4 and 5 min, respectively. Next-generations sequencing revealed that VpP1 (63,510 bp) and VpP2 (64,298 bp) did not contain known virulence, antibiotic-resistance or lysogenic genes, highlighting their capability to be used as biocontrol agents. Phylogenetic analysis based on the major head protein revealed that VpP1 and VpP2 were categorised into the newly described <em>Mardecavirus</em> genus. The results suggest VpP1 and VpP2 have several beneficial qualities for future use as biocontrol agents. Further study is still required to determine their efficiency within food applications.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199664"},"PeriodicalIF":2.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533840","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 : 2025-11-09DOI: 10.1016/j.virusres.2025.199663
Fanhua Meng , Xuechun Liu , Yuqing Song , Xinbing Hu , Zhancheng Tian , Guiquan Guan , Lijie Tang , Hong Yin , Junzheng Du
Bluetongue (BT) is a severe infectious disease affecting ruminants, caused by the bluetongue virus (BTV), an Orbivirus transmitted by Culicoides midges. VP5 is a major component of the outer capsid of BTV, and a key constituent of BTV subunit and virus-like particle vaccines. However, to date, the B-cell epitopes on VP5 recognized by humoral immune responses remain unidentified. In this study, recombinant VP5Δ1–79aa was expressed in Escherichia coli (E. coli) and purified for mouse immunization. Five monoclonal antibodies (mAbs) were identified through hybridoma fusion, clonal selection, and immunological assays. B-cell epitopes were recognized by mAbs 4G9, 6C9, 3A1, 3C8 and 6B1, these epitopes were mapped using a series of truncated overlapping peptides expressed as glutathione S-transferase fusion proteins. 4G9 recognized the 144DEKQFDILNK153 sequence, 6C9 recognized 154AVTSYNKILT163, 3A1 and 3C8 recognized 207VERDGMQEEA216, and 6B1 recognized 312ENHKELMHIK321. These specific mAbs and their corresponding B-cell epitopes provide valuable insights into the structure and function of VP5, contributing to the advancement of serological diagnostic methods and development of epitope-based vaccines for BTV.
{"title":"B-cell epitope mapping of VP5 protein of bluetongue virus serotype 1 using monoclonal antibodies","authors":"Fanhua Meng , Xuechun Liu , Yuqing Song , Xinbing Hu , Zhancheng Tian , Guiquan Guan , Lijie Tang , Hong Yin , Junzheng Du","doi":"10.1016/j.virusres.2025.199663","DOIUrl":"10.1016/j.virusres.2025.199663","url":null,"abstract":"<div><div>Bluetongue (BT) is a severe infectious disease affecting ruminants, caused by the bluetongue virus (BTV), an <em>Orbivirus</em> transmitted by <em>Culicoides</em> midges. VP5 is a major component of the outer capsid of BTV, and a key constituent of BTV subunit and virus-like particle vaccines. However, to date, the B-cell epitopes on VP5 recognized by humoral immune responses remain unidentified. In this study, recombinant VP5Δ1–79aa was expressed in <em>Escherichia coli</em> (<em>E. coli</em>) and purified for mouse immunization. Five monoclonal antibodies (mAbs) were identified through hybridoma fusion, clonal selection, and immunological assays. B-cell epitopes were recognized by mAbs 4G9, 6C9, 3A1, 3C8 and 6B1, these epitopes were mapped using a series of truncated overlapping peptides expressed as glutathione S-transferase fusion proteins. 4G9 recognized the <sup>144</sup>DEKQFDILNK<sup>153</sup> sequence, 6C9 recognized <sup>154</sup>AVTSYNKILT<sup>163</sup>, 3A1 and 3C8 recognized <sup>207</sup>VERDGMQEEA<sup>216</sup>, and 6B1 recognized <sup>312</sup>ENHKELMHIK<sup>321</sup>. These specific mAbs and their corresponding B-cell epitopes provide valuable insights into the structure and function of VP5, contributing to the advancement of serological diagnostic methods and development of epitope-based vaccines for BTV.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199663"},"PeriodicalIF":2.7,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496689","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 : 2025-11-05DOI: 10.1016/j.virusres.2025.199659
Aristide Mounchili-Njifon , Abdou Fatawou Modiyinji , Loique Landry E Messanga , Moise Henri Moumbeket Yifomnjou , Philipe Herman Njitoyap Mfombouot , Desmon Toutou Tsafack , Pretty Rosereine Mbouyap , Chavely Gwladys Monamele , Paul Alain Tagnouokam-Ngoupo , Simon Frederic Lissock , Jean Paul Assam Assam , Richard Njouom
In Cameroon, infection with the hepatitis C virus (HCV) is a major factor in hepatocellular carcinoma (HCC). Cirrhotic patients, even when treated with direct-acting antivirals (DAAs), may still be at risk of developing HCC. The aim of this study was to identify mutations associated with the development of HCC in treatment-naive HCV-infected patients, in order to understand the molecular mechanisms involved in this local context. From 2013 to 2023. 1065 HCV-infected Cameroonian patients provided blood samples. Plasma, isolated and stored at -80 °C, was used to amplify the Core gene using specific primers. Nucleotide sequences obtained by Sanger sequencing were analyzed with IQ-Tree for phylogenetic studies. Sequences were edited and aligned using Mega and MAFFT, and mutation searches were performed manually using AliView software. Three genotypes (1, 2, 4) were identified, with genotype 4 predominating. Several mutations known to play an oncogenic role were detected: K10R (0.66 %), R70Q (10.52 %), T72E (80.56 %), K74R (82.82 %), G77A (70.53 %) and C/L91M (0.09 %). A hundred other mutations potentially linked to response to AADs were also observed. The analysis revealed mutations significantly related to sex and year, such as (K115R, N106S, T48A) with p-values of (0.0023; 0.0006), (0.0012; 0.0004) and (0.0045; 0.0058) respectively. This study provides the first comprehensive mapping of HCV core mutations in Cameroon, identifying variants potentially linked to HCC. Although limited by the lack of clinical follow-up, it underscores the urgency of monitoring these mutations in national HCV elimination programs, in line with the WHO's goals for 2030.
{"title":"Identification of amino acid substitutions in the hepatitis C virus core region associated with the development of hepatocellular carcinoma in treatment-naive patients in Cameroon - a 10-year retrospective cross-sectional study","authors":"Aristide Mounchili-Njifon , Abdou Fatawou Modiyinji , Loique Landry E Messanga , Moise Henri Moumbeket Yifomnjou , Philipe Herman Njitoyap Mfombouot , Desmon Toutou Tsafack , Pretty Rosereine Mbouyap , Chavely Gwladys Monamele , Paul Alain Tagnouokam-Ngoupo , Simon Frederic Lissock , Jean Paul Assam Assam , Richard Njouom","doi":"10.1016/j.virusres.2025.199659","DOIUrl":"10.1016/j.virusres.2025.199659","url":null,"abstract":"<div><div>In Cameroon, infection with the hepatitis C virus (HCV) is a major factor in hepatocellular carcinoma (HCC). Cirrhotic patients, even when treated with direct-acting antivirals (DAAs), may still be at risk of developing HCC. The aim of this study was to identify mutations associated with the development of HCC in treatment-naive HCV-infected patients, in order to understand the molecular mechanisms involved in this local context. From 2013 to 2023. 1065 HCV-infected Cameroonian patients provided blood samples. Plasma, isolated and stored at -80 °C, was used to amplify the Core gene using specific primers. Nucleotide sequences obtained by Sanger sequencing were analyzed with IQ-Tree for phylogenetic studies. Sequences were edited and aligned using Mega and MAFFT, and mutation searches were performed manually using AliView software. Three genotypes (1, 2, 4) were identified, with genotype 4 predominating. Several mutations known to play an oncogenic role were detected: K10R (0.66 %), R70Q (10.52 %), T72E (80.56 %), K74R (82.82 %), G77A (70.53 %) and C/L91M (0.09 %). A hundred other mutations potentially linked to response to AADs were also observed. The analysis revealed mutations significantly related to sex and year, such as (K115R, N106S, T48A) with p-values of (0.0023; 0.0006), (0.0012; 0.0004) and (0.0045; 0.0058) respectively. This study provides the first comprehensive mapping of HCV core mutations in Cameroon, identifying variants potentially linked to HCC. Although limited by the lack of clinical follow-up, it underscores the urgency of monitoring these mutations in national HCV elimination programs, in line with the WHO's goals for 2030.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199659"},"PeriodicalIF":2.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468865","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 : 2025-11-04DOI: 10.1016/j.virusres.2025.199658
Mollie Curran-French , Jake D’Addiego , Stuart Dent , Gillian Slack , Kyle Perrins , Fern Jenkins , Nyah Davis , Roger Hewson
Two closely related tick-borne Orthoflaviviruses have been detected in the UK; tick-borne encephalitis virus (TBEV) and louping ill virus (LIV). Diagnosis of tick-borne encephalitis is achieved by detection of IgM/IgG antibodies using ELISA, Immunofluorescence, or by RT-PCR. High sequence and structural similarities between these viruses means they are hard to distinguish due to high cross-reactivity. We have developed a novel RT-qPCR assay using recently identified subtypes of TBEV in the UK and a probe incorporating locked nucleic acids, strengthening hybridisation between the probe and target RNA/DNA, resulting in greater discrimination between thermodynamically similar sequences. Cell-cultured virus extracts and an in vitro transcript of the NS1 gene were used for assay validation. TBEV was specifically detected to a sensitivity of 13 copies per reaction at 95 % confidence with 94 % efficiency. The assay showed no cross-reactivity to 10 Flavivirus RNA extracts tested. Of 43 clinical tick bite samples tested, 23 were TBEV seropositive and all tested negative by the currently used qPCR assay, matching our assay results. A sensitive, highly specific RT-qPCR assay that distinguishes between UK subtypes of TBEV and LIV. This distinction is vital for both accurate clinical diagnosis and vector surveillance, especially in the UK where both viruses co-circulate and cross-reactivity remains a significant diagnostic challenge.
{"title":"Novel quantitative and specific RT-qPCR assay for UK subtypes of European strain of Tick-borne encephalitis virus","authors":"Mollie Curran-French , Jake D’Addiego , Stuart Dent , Gillian Slack , Kyle Perrins , Fern Jenkins , Nyah Davis , Roger Hewson","doi":"10.1016/j.virusres.2025.199658","DOIUrl":"10.1016/j.virusres.2025.199658","url":null,"abstract":"<div><div>Two closely related tick-borne <em>Orthoflaviviruses</em> have been detected in the UK; tick-borne encephalitis virus (TBEV) and louping ill virus (LIV). Diagnosis of tick-borne encephalitis is achieved by detection of IgM/IgG antibodies using ELISA, Immunofluorescence, or by RT-PCR. High sequence and structural similarities between these viruses means they are hard to distinguish due to high cross-reactivity. We have developed a novel RT-qPCR assay using recently identified subtypes of TBEV in the UK and a probe incorporating locked nucleic acids, strengthening hybridisation between the probe and target RNA/DNA, resulting in greater discrimination between thermodynamically similar sequences. Cell-cultured virus extracts and an in vitro transcript of the NS1 gene were used for assay validation. TBEV was specifically detected to a sensitivity of 13 copies per reaction at 95 % confidence with 94 % efficiency. The assay showed no cross-reactivity to 10 Flavivirus RNA extracts tested. Of 43 clinical tick bite samples tested, 23 were TBEV seropositive and all tested negative by the currently used qPCR assay, matching our assay results. A sensitive, highly specific RT-qPCR assay that distinguishes between UK subtypes of TBEV and LIV. This distinction is vital for both accurate clinical diagnosis and vector surveillance, especially in the UK where both viruses co-circulate and cross-reactivity remains a significant diagnostic challenge.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199658"},"PeriodicalIF":2.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145449297","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 : 2025-11-03DOI: 10.1016/j.virusres.2025.199656
Weijun Cao , Jingwen Li , Fan Yang , Zixiang Zhu , Wei Zhang , Haixue Zheng , Yanming Wei
Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease. Traditional intramuscular (IM) injection of inactivated FMD vaccines has been crucial for disease control, but intradermal (ID) immunization offers advantages such as reduced vaccine dosage and decreased animal discomfort. The differences in immune efficiency of intradermal and intramuscular delivery of FMD commercial inactivated vaccine in pigs remain unclear. Here, we compared the immune efficacy of ID and IM immunization using the same dose of commercial FMD vaccine. Experimental pigs were administered the vaccine via either ID or IM routes. At 28 days post-immunization (dpi), the ID group produces less uniform levels of FMDV-specific antibodies than IM groups. The detection of IL-4, IL-6, and IFN-γ in porcine serum samples revealed a lower cellular immune response in the ID group as well in the early stages. Meanwhile, the IM group exhibited higher percentages of CD8+ T cells producing IFN-γ. These results indicate that, at the same dose of FMDV antigen emulsified with adjuvant ISA 201VG, initial humoral and cellular immune responses were weaker in the ID group compared to the IM group in the early stages, and the uniformity of antibody response levels was poorer in the ID group. While ID immunization holds promise for future vaccine strategies, its application with the current inactivated FMDV vaccine carries a higher risk of immunization failure due to the heterogeneity of immune responses.
{"title":"Comparative investigation into the immune efficiency of the single intradermal and intramuscular delivery of foot-and-mouth disease inactivated vaccine in swine","authors":"Weijun Cao , Jingwen Li , Fan Yang , Zixiang Zhu , Wei Zhang , Haixue Zheng , Yanming Wei","doi":"10.1016/j.virusres.2025.199656","DOIUrl":"10.1016/j.virusres.2025.199656","url":null,"abstract":"<div><div>Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease. Traditional intramuscular (IM) injection of inactivated FMD vaccines has been crucial for disease control, but intradermal (ID) immunization offers advantages such as reduced vaccine dosage and decreased animal discomfort. The differences in immune efficiency of intradermal and intramuscular delivery of FMD commercial inactivated vaccine in pigs remain unclear. Here, we compared the immune efficacy of ID and IM immunization using the same dose of commercial FMD vaccine. Experimental pigs were administered the vaccine via either ID or IM routes. At 28 days post-immunization (dpi), the ID group produces less uniform levels of FMDV-specific antibodies than IM groups. The detection of IL-4, IL-6, and IFN-γ in porcine serum samples revealed a lower cellular immune response in the ID group as well in the early stages. Meanwhile, the IM group exhibited higher percentages of CD8<sup>+</sup> T cells producing IFN-γ. These results indicate that, at the same dose of FMDV antigen emulsified with adjuvant ISA 201VG, initial humoral and cellular immune responses were weaker in the ID group compared to the IM group in the early stages, and the uniformity of antibody response levels was poorer in the ID group. While ID immunization holds promise for future vaccine strategies, its application with the current inactivated FMDV vaccine carries a higher risk of immunization failure due to the heterogeneity of immune responses.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199656"},"PeriodicalIF":2.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452948","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}
HBV infection is a major global health concern, leading to numerous HBV-related deaths. Due to the lack of curative or eradicative treatments for HBV, a large number of individuals in the general population are at risk of HBV reactivation. The increasing application of ICIs for treating various malignancies has raised concerns about HBV reactivation caused by these therapies. HBV reactivation complicates the treatments, leading to the interruption or modification of therapeutic regimens, which presents a considerable challenge. In this review, we summarize relevant researches on the definition, prevalence, and pathogenesis of HBV reactivation. Furthermore, we discuss the risks and mechanism of HBV reactivation during ICIs treatment, outline management strategies for HBV reactivation, and provide recommendations for assessing and monitoring HBV status during the treatment process.
{"title":"Antineoplastic agents-associated hepatitis B virus reactivation: Research progress and molecular mechanisms","authors":"Huajie Xie, Meijun Lv, Qin Jia, Yanyan Wang, Wanlin Na, Yuan Liu, Kai Chang","doi":"10.1016/j.virusres.2025.199655","DOIUrl":"10.1016/j.virusres.2025.199655","url":null,"abstract":"<div><div>HBV infection is a major global health concern, leading to numerous HBV-related deaths. Due to the lack of curative or eradicative treatments for HBV, a large number of individuals in the general population are at risk of HBV reactivation. The increasing application of ICIs for treating various malignancies has raised concerns about HBV reactivation caused by these therapies. HBV reactivation complicates the treatments, leading to the interruption or modification of therapeutic regimens, which presents a considerable challenge. In this review, we summarize relevant researches on the definition, prevalence, and pathogenesis of HBV reactivation. Furthermore, we discuss the risks and mechanism of HBV reactivation during ICIs treatment, outline management strategies for HBV reactivation, and provide recommendations for assessing and monitoring HBV status during the treatment process.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199655"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439175","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.2025.199654
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}
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