Pub Date : 2025-01-20DOI: 10.1016/j.virol.2025.110402
Claudia Alejandra Kornuta , Juan Esteban Bidart , Ivana Soria , Valeria Quattrocchi , Mariela Gammella , María Virginia Tribulatti , Oscar Campetella , Cecilia Arahí Prato , Julieta Carabelli , Felipe Andrés Cheuquepán , Yanina Paola Hecker , Prando Dadin Moore , Patricia Inés Zamorano , Cecilia Ana Langellotti
Bovine alphaherpesvirus-1 (BoAHV-1) causes several symptoms in cattle, leading to significant costs for the livestock industry. In this study, we used a plasmid encoding a secreted form of BoAHV-1 glycoprotein D (pCIgD) as a DNA vaccine. To enhance the potency of the pCIgD vaccine, we used Montanide™ GEL01 PR (GEL01) and introduced Galectin-8 (Gal-8), a lectin considered a novel adjuvant due to its immunostimulatory effects, into the formulation.
Animals were vaccinated with pCIgD, pCIgD with Gal-8 (pCIgD-Gal-8), pCIgD with Gal-8 and GEL01 (pCIgD-Gal-8-GEL01), or the control plasmid pCIneo. The immune response was first assessed in a mouse model and then in bovines.
The results showed that combining Gal-8 and GEL01 with pCIgD modulated immune responses at both the humoral and cellular levels in both animal models.
This study evaluates the efficacy of a DNA vaccine with Gal-8 and GEL01 as potential adjuvants to enhance immune protection against BoAHV-1.
{"title":"Galectin-8 and GEL01 as potential adjuvants to enhance the immune response induced by a DNA vaccine against bovine alphaherpesvirus Type-1","authors":"Claudia Alejandra Kornuta , Juan Esteban Bidart , Ivana Soria , Valeria Quattrocchi , Mariela Gammella , María Virginia Tribulatti , Oscar Campetella , Cecilia Arahí Prato , Julieta Carabelli , Felipe Andrés Cheuquepán , Yanina Paola Hecker , Prando Dadin Moore , Patricia Inés Zamorano , Cecilia Ana Langellotti","doi":"10.1016/j.virol.2025.110402","DOIUrl":"10.1016/j.virol.2025.110402","url":null,"abstract":"<div><div>Bovine alphaherpesvirus-1 (BoAHV-1) causes several symptoms in cattle, leading to significant costs for the livestock industry. In this study, we used a plasmid encoding a secreted form of BoAHV-1 glycoprotein D (pCIgD) as a DNA vaccine. To enhance the potency of the pCIgD vaccine, we used Montanide™ GEL01 PR (GEL01) and introduced Galectin-8 (Gal-8), a lectin considered a novel adjuvant due to its immunostimulatory effects, into the formulation.</div><div>Animals were vaccinated with pCIgD, pCIgD with Gal-8 (pCIgD-Gal-8), pCIgD with Gal-8 and GEL01 (pCIgD-Gal-8-GEL01), or the control plasmid pCIneo. The immune response was first assessed in a mouse model and then in bovines.</div><div>The results showed that combining Gal-8 and GEL01 with pCIgD modulated immune responses at both the humoral and cellular levels in both animal models.</div><div>This study evaluates the efficacy of a DNA vaccine with Gal-8 and GEL01 as potential adjuvants to enhance immune protection against BoAHV-1.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110402"},"PeriodicalIF":2.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-19DOI: 10.1016/j.virol.2025.110412
Mario Fragoso-Saavedra , Qiang Liu
Porcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.
{"title":"Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies","authors":"Mario Fragoso-Saavedra , Qiang Liu","doi":"10.1016/j.virol.2025.110412","DOIUrl":"10.1016/j.virol.2025.110412","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110412"},"PeriodicalIF":2.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-18DOI: 10.1016/j.virol.2025.110415
Soak Kuan Lai , Zhi Qi Lee , Trina Isabel Tan , Boon Huan Tan , Richard J. Sugrue
We examined how respiratory syncytial virus (RSV) particles circumvent the overlying glycocalyx on virus-infected A549 cells. The glycocalyx was detected using the lectin WGA-AL488 probe, and the antibodies anti-HS and anti-syndecan-4 that detect heparin sulphate (HS) and the syndecan-4 protein (SYND4) respectively. Imaging of RSV-infected cells provided evidence that the glycocalyx envelopes the virus filaments as they form, and that components of the glycocalyx such as HS moieties and SYND4 are displayed on the surface of the mature virus filaments. Recombinant expression of the G protein in these cells suggested that the G protein was trafficked into pre-existing filamentous cellular structures with a well-defined glycocalyx, further suggesting that the glycocalyx is maintained at the site of virus particle assembly. These data provide evidence that during RSV particle assembly the virus filaments become enveloped by the glycocalyx, and that the glycocalyx should be considered as a structural component of virus filaments.
{"title":"Evidence that the cell glycocalyx envelops respiratory syncytial virus (RSV) particles that form on the surface of RSV-infected human airway cells","authors":"Soak Kuan Lai , Zhi Qi Lee , Trina Isabel Tan , Boon Huan Tan , Richard J. Sugrue","doi":"10.1016/j.virol.2025.110415","DOIUrl":"10.1016/j.virol.2025.110415","url":null,"abstract":"<div><div>We examined how respiratory syncytial virus (RSV) particles circumvent the overlying glycocalyx on virus-infected A549 cells. The glycocalyx was detected using the lectin WGA-AL488 probe, and the antibodies anti-HS and anti-syndecan-4 that detect heparin sulphate (HS) and the syndecan-4 protein (SYND4) respectively. Imaging of RSV-infected cells provided evidence that the glycocalyx envelopes the virus filaments as they form, and that components of the glycocalyx such as HS moieties and SYND4 are displayed on the surface of the mature virus filaments. Recombinant expression of the G protein in these cells suggested that the G protein was trafficked into pre-existing filamentous cellular structures with a well-defined glycocalyx, further suggesting that the glycocalyx is maintained at the site of virus particle assembly. These data provide evidence that during RSV particle assembly the virus filaments become enveloped by the glycocalyx, and that the glycocalyx should be considered as a structural component of virus filaments.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110415"},"PeriodicalIF":2.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143178776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-17DOI: 10.1016/j.virol.2025.110414
Hershna Patel, Andreas Kukol
This mini-review examines the strategy of combining viral protein sequence conservation with drug-binding potential to identify novel antiviral targets, focusing on internal proteins of influenza A and other RNA viruses. The importance of combating viral genetic variability and reducing the likelihood of resistance development is emphasised in the context of sequence redundancy in viral datasets. It covers recent structural and functional updates, as well as drug targeting efforts for three internal influenza A viral proteins: Basic Polymerase 2, Nuclear Export Protein, and Nucleoprotein. The review discusses new insights into protein interactions, potential inhibitors, and recent drug discovery efforts. Similar approaches beyond influenza including Hepatitis E, SARS-CoV-2, Dengue, and the HIV-1 virus are also covered briefly.
{"title":"Harnessing viral internal proteins to combat flu and beyond","authors":"Hershna Patel, Andreas Kukol","doi":"10.1016/j.virol.2025.110414","DOIUrl":"10.1016/j.virol.2025.110414","url":null,"abstract":"<div><div>This mini-review examines the strategy of combining viral protein sequence conservation with drug-binding potential to identify novel antiviral targets, focusing on internal proteins of influenza A and other RNA viruses. The importance of combating viral genetic variability and reducing the likelihood of resistance development is emphasised in the context of sequence redundancy in viral datasets. It covers recent structural and functional updates, as well as drug targeting efforts for three internal influenza A viral proteins: Basic Polymerase 2, Nuclear Export Protein, and Nucleoprotein. The review discusses new insights into protein interactions, potential inhibitors, and recent drug discovery efforts. Similar approaches beyond influenza including Hepatitis E, SARS-CoV-2, Dengue, and the HIV-1 virus are also covered briefly.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110414"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human coronaviruses (HCoVs) include common cold viruses such as HCoV-229E, OC43, NL63 and HKU1 as well as MERS-CoV and SARS-CoV, which cause severe respiratory disease. Recently, SARS-CoV-2 caused a COVID-19 pandemic. The nucleocapsid (N) protein of coronaviruses, which is essential for RNA binding and homodimerization, has a highly conserved structure across viruses. Previous studies revealed that compound PJ34 is an inhibitor of nucleic acid binding to the N-terminal domain (NTD) of the HCoV-OC43 N protein, suggesting that it could block viral replication. However, testing with SARS-CoV-2 showed that PJ34 did not inhibit viral replication. Structural analysis suggests that the substitution of Tyr for Ala at position 50 (corresponding to Tyr63 in OC43), may affect the ability to interact with compounds such as PJ34, explaining its lack of efficacy. These findings underscore the importance of structure-based drug development targeting the N protein, which remains an important therapeutic target in all coronaviruses.
{"title":"Structural insights into nucleocapsid protein variability: Implications for PJ34 efficacy against SARS-CoV-2","authors":"Akima Yamamoto, Haruki Ito, Takemasa Sakaguchi , Akifumi Higashiura","doi":"10.1016/j.virol.2025.110411","DOIUrl":"10.1016/j.virol.2025.110411","url":null,"abstract":"<div><div>Human coronaviruses (HCoVs) include common cold viruses such as HCoV-229E, OC43, NL63 and HKU1 as well as MERS-CoV and SARS-CoV, which cause severe respiratory disease. Recently, SARS-CoV-2 caused a COVID-19 pandemic. The nucleocapsid (N) protein of coronaviruses, which is essential for RNA binding and homodimerization, has a highly conserved structure across viruses. Previous studies revealed that compound PJ34 is an inhibitor of nucleic acid binding to the N-terminal domain (NTD) of the HCoV-OC43 N protein, suggesting that it could block viral replication. However, testing with SARS-CoV-2 showed that PJ34 did not inhibit viral replication. Structural analysis suggests that the substitution of Tyr for Ala at position 50 (corresponding to Tyr63 in OC43), may affect the ability to interact with compounds such as PJ34, explaining its lack of efficacy. These findings underscore the importance of structure-based drug development targeting the N protein, which remains an important therapeutic target in all coronaviruses.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110411"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-17DOI: 10.1016/j.virol.2025.110417
Xinjian Zhuang , Wenyi Zhang , Shuqi Xu , Wenxuan Yang , Jinlong Yin , Tong Zhou , Jiban K. Kundu , Kai Xu
Clover yellow vein virus (ClYVV), a potyvirus that infects various dicotyledonous plants, poses a significant threat to the cultivation of legumes. Although potyviral NIa-Pro was extensively studied in viral infection cycle and host antiviral responses, the contribution of NIa-Pro protease activity to virus systemic symptoms has not yet been reported. In this study, we developed infectious clones of a ClYVV isolated from Pisum sativum. The rescued ClYVV showed robust infectivity and induced obvious systemic mosaic and necrosis symptoms in the model host Nicotiana benthamiana and natural hosts Pisum sativum and Vicia faba. Using a potato virus X (PVX) vector to express 11 ClYVV proteins in N. benthamiana ectopically, we identified that NIa-Pro is the key determinant in inducing systemic symptoms and causes higher leaf ROS levels and cell death. Further, we found that the protease-inactive mutant NIa-ProC151A causes significantly reduced systemic symptoms when expressed via the PVX vector and does not induce higher cellular ROS levels and cell death when transiently overexpressed compared to wild-type NIa-Pro. Overall, this study provides evidence supporting that the protease activity of a potyvirus protein NIa-Pro directly contributes to the virus symptoms.
{"title":"Protease activity of NIa-Pro determines systemic pathogenicity of clover yellow vein virus","authors":"Xinjian Zhuang , Wenyi Zhang , Shuqi Xu , Wenxuan Yang , Jinlong Yin , Tong Zhou , Jiban K. Kundu , Kai Xu","doi":"10.1016/j.virol.2025.110417","DOIUrl":"10.1016/j.virol.2025.110417","url":null,"abstract":"<div><div>Clover yellow vein virus (ClYVV), a potyvirus that infects various dicotyledonous plants, poses a significant threat to the cultivation of legumes. Although potyviral NIa-Pro was extensively studied in viral infection cycle and host antiviral responses, the contribution of NIa-Pro protease activity to virus systemic symptoms has not yet been reported. In this study, we developed infectious clones of a ClYVV isolated from <em>Pisum sativum</em>. The rescued ClYVV showed robust infectivity and induced obvious systemic mosaic and necrosis symptoms in the model host <em>Nicotiana benthamiana</em> and natural hosts <em>Pisum sativum</em> and <em>Vicia faba</em>. Using a potato virus X (PVX) vector to express 11 ClYVV proteins in <em>N. benthamiana</em> ectopically, we identified that NIa-Pro is the key determinant in inducing systemic symptoms and causes higher leaf ROS levels and cell death. Further, we found that the protease-inactive mutant NIa-Pro<sup>C151A</sup> causes significantly reduced systemic symptoms when expressed via the PVX vector and does not induce higher cellular ROS levels and cell death when transiently overexpressed compared to wild-type NIa-Pro. Overall, this study provides evidence supporting that the protease activity of a potyvirus protein NIa-Pro directly contributes to the virus symptoms.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110417"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-17DOI: 10.1016/j.virol.2025.110399
Md Safiul Alam Bhuiyan , Suman Das Gupta , Juplikely James Silip , Saranika Talukder , Md Hakimul Haque , Jade K. Forwood , Subir Sarker
Infectious bronchitis virus (IBV), an avian coronavirus, member of the genus Gammacoronavirus, poses significant threats to poultry health, causing severe respiratory, reproductive, and renal infections. The genetic diversity of IBV, driven by mutations, recombination and deletions, has led to the emergence of numerous serotypes and genotypes, complicating both diagnosis and control measures. Rapid and accurate diagnostic tools are essential for effective disease management and minimizing economic losses. Conventional diagnostic methods, such as PCR, virus isolation, and serological assays, are hindered by limitations in sensitivity, specificity, and turnaround time. In contrast, innovative biosensor platforms employing advanced detection mechanisms-including electrochemical, optical, and piezoelectric sensors-offer a transformative solution. These technologies provide portable, highly sensitive, and rapid diagnostic platforms for IBV detection. Beyond addressing the challenges of conventional methods, these biosensor-based approaches facilitate real-time monitoring and enhance disease surveillance. This review highlights the transformative potential of biosensors and their integration into diagnostic strategies for avian coronavirus infections, presenting them as a promising alternative for precise and efficient IBV detection.
{"title":"Current trends and future potential in the detection of avian coronaviruses: An emphasis on sensors-based technologies","authors":"Md Safiul Alam Bhuiyan , Suman Das Gupta , Juplikely James Silip , Saranika Talukder , Md Hakimul Haque , Jade K. Forwood , Subir Sarker","doi":"10.1016/j.virol.2025.110399","DOIUrl":"10.1016/j.virol.2025.110399","url":null,"abstract":"<div><div>Infectious bronchitis virus (IBV), an avian coronavirus, member of the genus <em>Gammacoronavirus</em>, poses significant threats to poultry health, causing severe respiratory, reproductive, and renal infections. The genetic diversity of IBV, driven by mutations, recombination and deletions, has led to the emergence of numerous serotypes and genotypes, complicating both diagnosis and control measures. Rapid and accurate diagnostic tools are essential for effective disease management and minimizing economic losses. Conventional diagnostic methods, such as PCR, virus isolation, and serological assays, are hindered by limitations in sensitivity, specificity, and turnaround time. In contrast, innovative biosensor platforms employing advanced detection mechanisms-including electrochemical, optical, and piezoelectric sensors-offer a transformative solution. These technologies provide portable, highly sensitive, and rapid diagnostic platforms for IBV detection. Beyond addressing the challenges of conventional methods, these biosensor-based approaches facilitate real-time monitoring and enhance disease surveillance. This review highlights the transformative potential of biosensors and their integration into diagnostic strategies for avian coronavirus infections, presenting them as a promising alternative for precise and efficient IBV detection.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110399"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea death in newborn piglets, resulting in significant economic losses for the pig industry. Therefore, the advancement of safe and effective anti-PEDV drugs for the treatment of PEDV is of paramount importance. In this study, molecular docking was used to screen natural drugs that can target PEDV 3C like protease (3CLpro). As well, the anti-PEDV effects of the screened drugs were evaluated in vitro and in vivo. Molecular docking and molecular dynamics (MD) simulation results showed that ethyl caffeate (EC) could efficiently bind to the active cavity of PEDV 3CLpro. Biolayer interferometry (BLI) and fluorescence resonance energy transfer (FRET) analyses demonstrated that EC directly interacts with PEDV 3CLpro (KD = 1650 μM) and inhibits the activity of 3CLpro (IC50 = 33.87 μM). EC has been shown to significantly inhibit the replication of PEDV in Vero E6 cells. The half maximal inhibitory concentration (CC50) and half-effective concentration (EC50) were determined to be 283.1 μM and 8.641 μM, respectively, yielding a selectivity index as high as 32.7. Furthermore, EC was evaluated using a piglet infection model for PEDV. It demonstrated the ability to inhibit PEDV infection in vivo and improve the survival rate of piglets (3/5, 60%). Compared to the control group, oral administration of EC significantly reduced intestinal pathological damage and viral load. Our study indicated that EC, targeting PEDV 3CLpro, is a safe and effective anti-PEDV drug with promising clinical application prospects.
{"title":"Ethyl caffeate as a novel targeted inhibitor of 3CLpro with antiviral activity against porcine epidemic diarrhea virus","authors":"Limin Jiang , Minghui Gu , Jiawei Xiao, Yingying Zhao, Fanbo Shen, Xingyang Guo, Hansong Li, Donghua Guo, Chunqiu Li, Qinghe Zhu, Dan Yang, Xiaoxu Xing, Dongbo Sun","doi":"10.1016/j.virol.2025.110406","DOIUrl":"10.1016/j.virol.2025.110406","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea death in newborn piglets, resulting in significant economic losses for the pig industry. Therefore, the advancement of safe and effective anti-PEDV drugs for the treatment of PEDV is of paramount importance. In this study, molecular docking was used to screen natural drugs that can target PEDV 3C like protease (3CLpro). As well, the anti-PEDV effects of the screened drugs were evaluated <em>in vitro</em> and <em>in vivo</em>. Molecular docking and molecular dynamics (MD) simulation results showed that ethyl caffeate (EC) could efficiently bind to the active cavity of PEDV 3CLpro. Biolayer interferometry (BLI) and fluorescence resonance energy transfer (FRET) analyses demonstrated that EC directly interacts with PEDV 3CLpro (K<sub>D</sub> = 1650 μM) and inhibits the activity of 3CLpro (IC<sub>50</sub> = 33.87 μM). EC has been shown to significantly inhibit the replication of PEDV in Vero E6 cells. The half maximal inhibitory concentration (CC<sub>50</sub>) and half-effective concentration (EC<sub>50</sub>) were determined to be 283.1 μM and 8.641 μM, respectively, yielding a selectivity index as high as 32.7. Furthermore, EC was evaluated using a piglet infection model for PEDV. It demonstrated the ability to inhibit PEDV infection <em>in vivo</em> and improve the survival rate of piglets (3/5, 60%). Compared to the control group, oral administration of EC significantly reduced intestinal pathological damage and viral load. Our study indicated that EC, targeting PEDV 3CLpro, is a safe and effective anti-PEDV drug with promising clinical application prospects.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110406"},"PeriodicalIF":2.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1016/j.virol.2025.110409
Minting Ni , Shengyu Lin , Yongheng Shao , Jiao Tang , Shuxian Li , Chen Tan , Zhenli Gong , Hongbo Li , Jintao Wang , Guangliang Liu , Jianing Chen
Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family and causes respiratory symptoms in various animal species. Although the virus has been frequently detected among fecal samples, no study has described its infection of the intestine. Recently, diarrhea with low mortality has spread on pig farms in Gansu, China. Next-generation sequencing confirmed the emergence of PIV5 among the samples. The PIV5 strain was then successfully isolated and characterized in vitro. Further animal tests revealed that PIV5 can result in respiratory symptoms and mild diarrhea in piglets. Immunohistochemical staining confirmed PIV5 infection resulted in steatosis and contributed to diarrhea. A retrospective investigation revealed that the number of cases of PIV5 infection has increased since 2020. Overall, our study is the first to present data indicating that PIV5 infection leads to diarrhea. Although it has low pathogenicity, PIV5 may pose a potential threat to pig production in China.
{"title":"Enteric pathogenicity characterization of emerging parainfluenza virus 5 in western China","authors":"Minting Ni , Shengyu Lin , Yongheng Shao , Jiao Tang , Shuxian Li , Chen Tan , Zhenli Gong , Hongbo Li , Jintao Wang , Guangliang Liu , Jianing Chen","doi":"10.1016/j.virol.2025.110409","DOIUrl":"10.1016/j.virol.2025.110409","url":null,"abstract":"<div><div>Parainfluenza virus 5 (PIV5) is a member of the <em>Paramyxoviridae</em> family and causes respiratory symptoms in various animal species. Although the virus has been frequently detected among fecal samples, no study has described its infection of the intestine. Recently, diarrhea with low mortality has spread on pig farms in Gansu, China. Next-generation sequencing confirmed the emergence of PIV5 among the samples. The PIV5 strain was then successfully isolated and characterized in vitro. Further animal tests revealed that PIV5 can result in respiratory symptoms and mild diarrhea in piglets. Immunohistochemical staining confirmed PIV5 infection resulted in steatosis and contributed to diarrhea. A retrospective investigation revealed that the number of cases of PIV5 infection has increased since 2020. Overall, our study is the first to present data indicating that PIV5 infection leads to diarrhea. Although it has low pathogenicity, PIV5 may pose a potential threat to pig production in China.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110409"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.virol.2025.110407
Ruiming Yu , Liping Zhang , Dongsheng Wang , Jun Yang , Peng Zhou , Yuhan Wen , Mingxia Li , Yingjie Bai , Zhongwang Zhang , Yousheng Peng , Yanzhen Lu , Dan Li , Jian He , Yonglu Wang , Huichen Guo , Li Pan , Xinsheng Liu
Porcine epidemic diarrhea virus (PEDV) has caused significant harm to the global pig industry since its discovery. In this study, a highly pathogenic strain of GIIa PEDV CH/HBXT/2018, isolated previously, was continuously passaged in Vero cells up to passage (P)240, resulting in a completely attenuated virus. The proliferation characteristics of different passages of the strain in Vero cells, pathogenicity in newborn piglets, and mutations in S gene sequence indicated that as the passage number increased, the replication efficiency of PEDV in Vero cells gradually improved, with a more pronounced cytopathic effect. However, its pathogenicity in piglets decreased progressively, evident as reduced viral loads in the feces and intestinal tissues, less-severe clinical symptoms, less-severe histopathological damage, and lower antigen expression in intestinal tissues. At P240, the strain was completely attenuated. A sequence analysis revealed 17 amino acid mutations in the structural spike protein, which may have contributed to the biological changes observed at P240. Furthermore, compared with P10, the strain's dependence on trypsin had decreased significantly at P200. A differential transcriptomic analysis revealed 1712 differentially expressed genes (DEGs) between the P10 and P200 infection groups, of which 458 were upregulated and 1254 downregulated. These DEGs were primarily involved in signaling pathways such as cytokine–cytokine receptor interaction, inflammatory response, and MHC protein complex. Our findings provide valuable insights into the mechanisms of PEDV attenuation and should facilitate the development of live vaccines.
{"title":"Characterization of a cell-adapted completely attenuated genotype GIIa porcine epidemic diarrhea virus strain","authors":"Ruiming Yu , Liping Zhang , Dongsheng Wang , Jun Yang , Peng Zhou , Yuhan Wen , Mingxia Li , Yingjie Bai , Zhongwang Zhang , Yousheng Peng , Yanzhen Lu , Dan Li , Jian He , Yonglu Wang , Huichen Guo , Li Pan , Xinsheng Liu","doi":"10.1016/j.virol.2025.110407","DOIUrl":"10.1016/j.virol.2025.110407","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) has caused significant harm to the global pig industry since its discovery. In this study, a highly pathogenic strain of GIIa PEDV CH/HBXT/2018, isolated previously, was continuously passaged in Vero cells up to passage (P)240, resulting in a completely attenuated virus. The proliferation characteristics of different passages of the strain in Vero cells, pathogenicity in newborn piglets, and mutations in S gene sequence indicated that as the passage number increased, the replication efficiency of PEDV in Vero cells gradually improved, with a more pronounced cytopathic effect. However, its pathogenicity in piglets decreased progressively, evident as reduced viral loads in the feces and intestinal tissues, less-severe clinical symptoms, less-severe histopathological damage, and lower antigen expression in intestinal tissues. At P240, the strain was completely attenuated. A sequence analysis revealed 17 amino acid mutations in the structural spike protein, which may have contributed to the biological changes observed at P240. Furthermore, compared with P10, the strain's dependence on trypsin had decreased significantly at P200. A differential transcriptomic analysis revealed 1712 differentially expressed genes (DEGs) between the P10 and P200 infection groups, of which 458 were upregulated and 1254 downregulated. These DEGs were primarily involved in signaling pathways such as cytokine–cytokine receptor interaction, inflammatory response, and MHC protein complex. Our findings provide valuable insights into the mechanisms of PEDV attenuation and should facilitate the development of live vaccines.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"604 ","pages":"Article 110407"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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