Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199671
Kangli Li , Boning Zhu , Shuo Wang , Xiangle Zhang , Xiaodan Wen , Weijun Cao , Guoliang Zhu , Haixue Zheng , Fan Yang , Zixiang Zhu
Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease (FMD), which is highly contagious and extremely destructive in cloven-hoofed animals. Previous studies have shown that FMDV strongly suppress the innate immune response, and the research mainly focused on FMDV 3C and L proteinase. However, the role of FMDV 3D polymerase, an RNA-dependent RNA polymerase (RdRp), in inhibiting the IFN signaling pathway remains unclear. In this study, for the first time, we demonstrate that the highly conserved 3D polymerase of FMDV inhibits the activation of the JAK-STAT signaling pathway by targeting STAT2. Mechanistically, FMDV 3D significantly inhibits the activity of the interferon-stimulated response element promoter and downregulates the transcription of interferon-stimulated genes. Further research revealed that 3D interacts with STAT2, hinders its phosphorylation, and inhibits its nuclear translocation, thereby blocking the activation of the JAK-STAT signaling pathway. Collectively, these findings elucidate a novel mechanism by which FMDV 3D polymerase, acting as an inhibitor, targets STAT2 to suppress IFN signaling and antagonize the host antiviral immune response. This will provide insights for the development of future anti-FMDV strategies.
{"title":"Foot-and-mouth disease virus 3D polymerase antagonizes the interferon signaling pathway by blocking STAT2 nuclear translocation","authors":"Kangli Li , Boning Zhu , Shuo Wang , Xiangle Zhang , Xiaodan Wen , Weijun Cao , Guoliang Zhu , Haixue Zheng , Fan Yang , Zixiang Zhu","doi":"10.1016/j.virusres.2025.199671","DOIUrl":"10.1016/j.virusres.2025.199671","url":null,"abstract":"<div><div>Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease (FMD), which is highly contagious and extremely destructive in cloven-hoofed animals. Previous studies have shown that FMDV strongly suppress the innate immune response, and the research mainly focused on FMDV 3C and L proteinase. However, the role of FMDV 3D polymerase, an RNA-dependent RNA polymerase (RdRp), in inhibiting the IFN signaling pathway remains unclear. In this study, for the first time, we demonstrate that the highly conserved 3D polymerase of FMDV inhibits the activation of the JAK-STAT signaling pathway by targeting STAT2. Mechanistically, FMDV 3D significantly inhibits the activity of the interferon-stimulated response element promoter and downregulates the transcription of interferon-stimulated genes. Further research revealed that 3D interacts with STAT2, hinders its phosphorylation, and inhibits its nuclear translocation, thereby blocking the activation of the JAK-STAT signaling pathway. Collectively, these findings elucidate a novel mechanism by which FMDV 3D polymerase, acting as an inhibitor, targets STAT2 to suppress IFN signaling and antagonize the host antiviral immune response. This will provide insights for the development of future anti-FMDV strategies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"363 ","pages":"Article 199671"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669507","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 : 2025-12-01DOI: 10.1016/j.virusres.2025.199660
I-Na Lu , Claude P. Muller , Feng Q. HeFeng
{"title":"Corrigendum to “Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies” [Virus Research, 283 (2020) 197963]","authors":"I-Na Lu , Claude P. Muller , Feng Q. HeFeng","doi":"10.1016/j.virusres.2025.199660","DOIUrl":"10.1016/j.virusres.2025.199660","url":null,"abstract":"","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199660"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530915","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 : 2025-12-01DOI: 10.1016/j.virusres.2025.199667
Liaofu Luo , Jun Lv
Predicting the future evolutionary trajectory of SARS-CoV-2 remains a critical challenge, particularly due to the pivotal role of spike protein mutations. It is therefore essential to develop evolutionary models capable of continuously integrating new experimental data. In this study, we employ a cladogram algorithm that incorporates established assumptions for mutant representation — using both four-letter and two-letter formats — along with an n-mer distance algorithm to construct a cladogenetic tree of SARS-CoV-2 mutations. This tree accurately captures the observed changes across macro-lineages. We introduce a stochastic method for generating new strains on this tree based on spike protein mutations. For a given set A of existing mutation sites, we define a set X comprising x randomly generated mutation sites on the spike protein. The intersection of A and X, denoted as set Y, contains y sites. Our analysis indicates that the position of a generated strain on the tree is primarily determined by x. Through large-scale stochastic sampling, we predict the emergence of new macro-lineages. As x increases, the dominance among macro-lineages shifts: lineage O surpasses N, P surpasses O, and eventually Q surpasses P. We identify threshold values of x that delineate transitions between these macro-lineages. Furthermore, we propose an algorithm for predicting the timeline of macro-lineage emergence. In conclusion, our findings demonstrate that SARS-CoV-2 evolution adheres to statistical principles: the emergence of new strains can be driven by randomly generated spike protein sites, and large-scale stochastic sampling reveals evolutionary patterns underlying the rise of distinct macro-lineages.
{"title":"Stochastic mutation as a mechanism for the emergence of SARS-CoV-2 new variants","authors":"Liaofu Luo , Jun Lv","doi":"10.1016/j.virusres.2025.199667","DOIUrl":"10.1016/j.virusres.2025.199667","url":null,"abstract":"<div><div>Predicting the future evolutionary trajectory of SARS-CoV-2 remains a critical challenge, particularly due to the pivotal role of spike protein mutations. It is therefore essential to develop evolutionary models capable of continuously integrating new experimental data. In this study, we employ a cladogram algorithm that incorporates established assumptions for mutant representation — using both four-letter and two-letter formats — along with an <em>n</em>-mer distance algorithm to construct a cladogenetic tree of SARS-CoV-2 mutations. This tree accurately captures the observed changes across macro-lineages. We introduce a stochastic method for generating new strains on this tree based on spike protein mutations. For a given set <em>A</em> of existing mutation sites, we define a set <em>X</em> comprising <em>x</em> randomly generated mutation sites on the spike protein. The intersection of <em>A</em> and <em>X</em>, denoted as set <em>Y</em>, contains <em>y</em> sites. Our analysis indicates that the position of a generated strain on the tree is primarily determined by <em>x</em>. Through large-scale stochastic sampling, we predict the emergence of new macro-lineages. As <em>x</em> increases, the dominance among macro-lineages shifts: lineage O surpasses N, P surpasses O, and eventually Q surpasses P. We identify threshold values of <em>x</em> that delineate transitions between these macro-lineages. Furthermore, we propose an algorithm for predicting the timeline of macro-lineage emergence. In conclusion, our findings demonstrate that SARS-CoV-2 evolution adheres to statistical principles: the emergence of new strains can be driven by randomly generated spike protein sites, and large-scale stochastic sampling reveals evolutionary patterns underlying the rise of distinct macro-lineages.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199667"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582297","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 : 2025-11-16DOI: 10.1016/j.virusres.2025.199665
Abbas Khan , Anwar Mohammad , Fahad M. Alshabrmi , Eid A. Alatawi , Muhammad Junaid , Abdelali Agouni
Human metapneumovirus (HMPV), a current escalating health issue, causes respiratory complications in young children, the elderly, and immunocompromised individuals. To date, no specific treatment is available; thus, to support vaccine and therapeutic development, we present HMPV-TherRes: a specialized database for HMPV research. This platform integrates a wealth of genomic, proteomic, structural, and immunological data, as well as target-specific drugs, RNA-based therapeutics, and CRISPR-based designs, offering an invaluable resource for advancing both basic and clinical research. The database integrates data generated through state-of-the-art and AI-powered algorithms. The database hosts 618 annotated genomes from various parts of the world, along with protein information, including their physicochemical properties, and experimentally derived or AlphaFold-predicted 3D structures. Moreover, immune resources are a central feature, encompassing detailed information on the predicted and experimentally reported cytotoxic T lymphocyte (CTL) epitopes, helper T lymphocyte (HTL) epitopes (IFN ±), and B-cell epitopes. Additionally, it includes curated datasets, multi-epitope vaccines, and mRNA-based vaccine candidates, underscoring its utility in vaccine design and development. The database also provides data on different drugs targeting hMPV, along with extensive RNA-therapeutic resources, such as siRNAs and miRNAs, which are instrumental in gene-silencing applications. Further expanding its scope, HMPV-TherRes includes CRISPR-based sgRNA designs for both Cas9 and Cas13, enabling targeted genome editing and regulation of the transcriptome. HMPV-TherRes is a versatile repository bridging experimental and computational studies, consolidating diverse resources to support vaccine design, RNA therapeutics, and drug development. It advances understanding of hMPV biology, accelerating efforts to combat the pathogen. This centralized, user-friendly platform represents a significant advancement in virology, enabling researchers to develop novel interventions against HMPV. The database can be accessed through: https://ddd.agounikhanlabs.com/hmpvetherpresdb/index.php.
{"title":"HMPV-TherResDB: Comprehensive human metapneumovirus (HMPV) database for sequence-structure annotations, vaccine resources, and therapeutics research","authors":"Abbas Khan , Anwar Mohammad , Fahad M. Alshabrmi , Eid A. Alatawi , Muhammad Junaid , Abdelali Agouni","doi":"10.1016/j.virusres.2025.199665","DOIUrl":"10.1016/j.virusres.2025.199665","url":null,"abstract":"<div><div>Human metapneumovirus (HMPV), a current escalating health issue, causes respiratory complications in young children, the elderly, and immunocompromised individuals. To date, no specific treatment is available; thus, to support vaccine and therapeutic development, we present HMPV-TherRes: a specialized database for HMPV research. This platform integrates a wealth of genomic, proteomic, structural, and immunological data, as well as target-specific drugs, RNA-based therapeutics, and CRISPR-based designs, offering an invaluable resource for advancing both basic and clinical research. The database integrates data generated through state-of-the-art and AI-powered algorithms. The database hosts 618 annotated genomes from various parts of the world, along with protein information, including their physicochemical properties, and experimentally derived or AlphaFold-predicted 3D structures. Moreover, immune resources are a central feature, encompassing detailed information on the predicted and experimentally reported cytotoxic T lymphocyte (CTL) epitopes, helper T lymphocyte (HTL) epitopes (IFN ±), and B-cell epitopes. Additionally, it includes curated datasets, multi-epitope vaccines, and mRNA-based vaccine candidates, underscoring its utility in vaccine design and development. The database also provides data on different drugs targeting hMPV, along with extensive RNA-therapeutic resources, such as siRNAs and miRNAs, which are instrumental in gene-silencing applications. Further expanding its scope, HMPV-TherRes includes CRISPR-based sgRNA designs for both Cas9 and Cas13, enabling targeted genome editing and regulation of the transcriptome. HMPV-TherRes is a versatile repository bridging experimental and computational studies, consolidating diverse resources to support vaccine design, RNA therapeutics, and drug development. It advances understanding of hMPV biology, accelerating efforts to combat the pathogen. This centralized, user-friendly platform represents a significant advancement in virology, enabling researchers to develop novel interventions against HMPV. The database can be accessed through: <span><span>https://ddd.agounikhanlabs.com/hmpvetherpresdb/index.php</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"363 ","pages":"Article 199665"},"PeriodicalIF":2.7,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551137","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 : 2025-11-14DOI: 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.
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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}
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