Pub Date : 2024-11-16DOI: 10.1016/j.virol.2024.110308
Guangyu Guo , Zhi Liu , Jiamin Zeng , Hongyu Yan , Gongrui Chen , Peiyun Han , Xinyi He , Dandan Zhou , Shaoping Weng , Jianguo He , Muhua Wang
The red swamp crayfish (Procambarus clarkii) is the second most widely cultured crustacean globally. As a highly invasive species with a worldwide distribution, P. clarkii presents a substantial risk for the transmission of viral pathogens to native aquatic organisms. Recently, the emergence of growth retardation disease (GRD) in P. clarkii has led to significant production declines and economic losses. A comprehensive viromic analysis could offer valuable insights into the potential viral pathogens harbored by P. clarkii. Here we systematically examined the RNA viromes of healthy and GRD-affected P. clarkii collected from Qianjiang, China. Our investigation identified a total of 1729 viral species across 21 known viral taxa, with 1603 species being previously unreported. The orders Picornavirales, Tolivirales, and Nodamuvirales were predominant in both species count and relative abundance. Moreover, seven viruses exhibited higher abundance in GRD-affected P. clarkii compared to healthy individuals. Our work uncovers an unexpectedly diverse RNA viral community within P. clarkii and identifies potential viral pathogens associated with GRD in this species.
{"title":"Virome analysis unveils a rich array of newly identified viruses in the red swamp crayfish Procambarus clarkii","authors":"Guangyu Guo , Zhi Liu , Jiamin Zeng , Hongyu Yan , Gongrui Chen , Peiyun Han , Xinyi He , Dandan Zhou , Shaoping Weng , Jianguo He , Muhua Wang","doi":"10.1016/j.virol.2024.110308","DOIUrl":"10.1016/j.virol.2024.110308","url":null,"abstract":"<div><div>The red swamp crayfish (<em>Procambarus clarkii</em>) is the second most widely cultured crustacean globally. As a highly invasive species with a worldwide distribution, <em>P. clarkii</em> presents a substantial risk for the transmission of viral pathogens to native aquatic organisms. Recently, the emergence of growth retardation disease (GRD) in <em>P. clarkii</em> has led to significant production declines and economic losses. A comprehensive viromic analysis could offer valuable insights into the potential viral pathogens harbored by <em>P. clarkii</em>. Here we systematically examined the RNA viromes of healthy and GRD-affected <em>P. clarkii</em> collected from Qianjiang, China. Our investigation identified a total of 1729 viral species across 21 known viral taxa, with 1603 species being previously unreported. The orders <em>Picornavirales</em>, <em>Tolivirales</em>, and <em>Nodamuvirales</em> were predominant in both species count and relative abundance. Moreover, seven viruses exhibited higher abundance in GRD-affected <em>P. clarkii</em> compared to healthy individuals. Our work uncovers an unexpectedly diverse RNA viral community within <em>P. clarkii</em> and identifies potential viral pathogens associated with GRD in this species.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110308"},"PeriodicalIF":2.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660779","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 : 2024-11-13DOI: 10.1016/j.virol.2024.110301
Shelby L. Brown, Jared P. May
Viral proteins with intrinsic disorder, such as the p26 movement protein from Pea enation mosaic virus 2 (PEMV2), can phase separate and form condensates that aid specific stages of virus replication. However, little is known about the impact of viral condensate formation on essential cellular processes, like translation. In this study, we performed mass spectrometry on affinity-purified p26 condensates and found an enrichment of RNA-binding proteins involved in translation and ribosome biogenesis. Puromycin assays and polysome profiling show that ectopic p26 expression suppresses ribosome assembly and translation in Nicotiana benthamiana, mirroring defects in late-stage PEMV2 infection. Despite interactions with the 2′-O-methyltransferase fibrillarin, p26 does not inhibit translation by altering rRNA methylation but instead binds directly to rRNAs and decreases their solubility. Disruption of ribosome assembly and translation by p26 during late PEMV2 infection may promote stages of the virus replication cycle that are incompatible with translation, including systemic movement.
{"title":"Viral condensates formed by Pea enation mosaic virus 2 sequester ribosomal components and suppress translation","authors":"Shelby L. Brown, Jared P. May","doi":"10.1016/j.virol.2024.110301","DOIUrl":"10.1016/j.virol.2024.110301","url":null,"abstract":"<div><div>Viral proteins with intrinsic disorder, such as the p26 movement protein from Pea enation mosaic virus 2 (PEMV2), can phase separate and form condensates that aid specific stages of virus replication. However, little is known about the impact of viral condensate formation on essential cellular processes, like translation. In this study, we performed mass spectrometry on affinity-purified p26 condensates and found an enrichment of RNA-binding proteins involved in translation and ribosome biogenesis. Puromycin assays and polysome profiling show that ectopic p26 expression suppresses ribosome assembly and translation in <em>Nicotiana benthamiana</em>, mirroring defects in late-stage PEMV2 infection. Despite interactions with the 2′-<em>O</em>-methyltransferase fibrillarin, p26 does not inhibit translation by altering rRNA methylation but instead binds directly to rRNAs and decreases their solubility. Disruption of ribosome assembly and translation by p26 during late PEMV2 infection may promote stages of the virus replication cycle that are incompatible with translation, including systemic movement.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110301"},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645321","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}
In our previous study, we established a method for purifying bacterially expressed HCV core 1–164 under non-denaturing conditions. In the present study, we elucidated the characteristics of the purified core. The purified HCV core exhibited a notable affinity for HCV RNA, with a Kd of 3 nM, as determined by a filter binding assay. Electron microscopy analysis revealed that the purified HCV core self-assembled with RNA into spherical structures approximately 50 nm in diameter. Additionally, we demonstrated the direct binding of the purified HCV core to the purified endoplasmic reticulum (ER). Moreover, lipid strip assays revealed specific binding of the purified HCV core to specific phospholipids, suggesting that the core plays a role in specific ER membrane domains. These studies reveal the biochemical characteristics of the HCV core that significantly advance our understanding of its role as a capsid protein in the viral lifecycle and pathogenesis.
{"title":"In vitro characteristics of purified recombinant hepatitis C virus core protein","authors":"Kyo Izumida , Yumiko Hara , Ryuta Iwatsuki , Sora Ohta , Keisuke Tabata , Eiji Morita","doi":"10.1016/j.virol.2024.110297","DOIUrl":"10.1016/j.virol.2024.110297","url":null,"abstract":"<div><div>In our previous study, we established a method for purifying bacterially expressed HCV core 1–164 under non-denaturing conditions. In the present study, we elucidated the characteristics of the purified core. The purified HCV core exhibited a notable affinity for HCV RNA, with a Kd of 3 nM, as determined by a filter binding assay. Electron microscopy analysis revealed that the purified HCV core self-assembled with RNA into spherical structures approximately 50 nm in diameter. Additionally, we demonstrated the direct binding of the purified HCV core to the purified endoplasmic reticulum (ER). Moreover, lipid strip assays revealed specific binding of the purified HCV core to specific phospholipids, suggesting that the core plays a role in specific ER membrane domains. These studies reveal the biochemical characteristics of the HCV core that significantly advance our understanding of its role as a capsid protein in the viral lifecycle and pathogenesis.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110297"},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635393","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}
Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the development of effective live-attenuated vaccines and antiviral strategies.
{"title":"Two amino acid pairs in the Gc glycoprotein of severe fever with thrombocytopenia syndrome virus responsible for the enhanced virulence","authors":"Shelly Wulandari , Samuel Nyampong , Michaela Beránková , Sithumini M.W. Lokupathirage , Kumiko Yoshimatsu , Hiroshi Shimoda , Daisuke Hayasaka","doi":"10.1016/j.virol.2024.110294","DOIUrl":"10.1016/j.virol.2024.110294","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the development of effective live-attenuated vaccines and antiviral strategies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110294"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635408","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 : 2024-11-05DOI: 10.1016/j.virol.2024.110285
Rokaia Sultana, Robert V. Stahelin
Virus-like particles (VLPs) resemble the parent virus but lack the viral genome, providing a safe and efficient platform for the analysis of virus assembly and budding as well as the development of vaccines and drugs. During the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the formation of SARS-CoV-2 VLPs was investigated as an alternative to authentic virions because the latter requires biosafety level 3 (BSL-3) facilities. This allowed researchers to model its assembly and budding processes, examine the role of mutations in variants of concern, and determine how the structural proteins interact with each other. Also, the absence of viral genome in VLPs circumvents worries of gains in infectivity via mutagenesis. This review summarizes the strengths and limitations of several SARS-CoV-2 VLP systems and details some of the strides that have been made in using these systems to study virus assembly and budding, viral entry, and antibody and vaccine development.
{"title":"Strengths and limitations of SARS-CoV-2 virus-like particle systems","authors":"Rokaia Sultana, Robert V. Stahelin","doi":"10.1016/j.virol.2024.110285","DOIUrl":"10.1016/j.virol.2024.110285","url":null,"abstract":"<div><div>Virus-like particles (VLPs) resemble the parent virus but lack the viral genome, providing a safe and efficient platform for the analysis of virus assembly and budding as well as the development of vaccines and drugs. During the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the formation of SARS-CoV-2 VLPs was investigated as an alternative to authentic virions because the latter requires biosafety level 3 (BSL-3) facilities. This allowed researchers to model its assembly and budding processes, examine the role of mutations in variants of concern, and determine how the structural proteins interact with each other. Also, the absence of viral genome in VLPs circumvents worries of gains in infectivity via mutagenesis. This review summarizes the strengths and limitations of several SARS-CoV-2 VLP systems and details some of the strides that have been made in using these systems to study virus assembly and budding, viral entry, and antibody and vaccine development.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110285"},"PeriodicalIF":2.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635402","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 : 2024-11-05DOI: 10.1016/j.virol.2024.110286
Sarah Neumeyer , Takanobu Tagawa
Kaposi sarcoma herpesvirus (KSHV) is an oncogenic DNA virus associated with various malignancies, including tumours like Kaposi sarcoma and Primary effusion lymphoma. Recently, the importance of the tumour microenvironment in KSHV-associated tumours is being studied. New studies utilizing human primary cells, co-culture experiments with KSHV-infected cells, and modern techniques like time-resolved single cell analysis, have significantly advanced the understanding of KSHV interactions with monocytes and macrophages. These cells play key roles in shaping the tumour microenvironment. It has become clear that KSHV-infected endothelial cells regulate the growth and the differentiation of monocytes and macrophages. Monocytes and macrophages, in turn, can regulate KSHV-infected cells in tumorigenesis and cytokine secretion, leading to the pro-tumour microenvironment. Further investigations into the viral regulation of monocytes and macrophages thus have potential to lead to the discovery of novel antitumour therapeutics.
{"title":"The Kaposi sarcoma herpesvirus control of monocytes, macrophages, and the tumour microenvironment","authors":"Sarah Neumeyer , Takanobu Tagawa","doi":"10.1016/j.virol.2024.110286","DOIUrl":"10.1016/j.virol.2024.110286","url":null,"abstract":"<div><div>Kaposi sarcoma herpesvirus (KSHV) is an oncogenic DNA virus associated with various malignancies, including tumours like Kaposi sarcoma and Primary effusion lymphoma. Recently, the importance of the tumour microenvironment in KSHV-associated tumours is being studied. New studies utilizing human primary cells, co-culture experiments with KSHV-infected cells, and modern techniques like time-resolved single cell analysis, have significantly advanced the understanding of KSHV interactions with monocytes and macrophages. These cells play key roles in shaping the tumour microenvironment. It has become clear that KSHV-infected endothelial cells regulate the growth and the differentiation of monocytes and macrophages. Monocytes and macrophages, in turn, can regulate KSHV-infected cells in tumorigenesis and cytokine secretion, leading to the pro-tumour microenvironment. Further investigations into the viral regulation of monocytes and macrophages thus have potential to lead to the discovery of novel antitumour therapeutics.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110286"},"PeriodicalIF":2.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635405","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 : 2024-11-04DOI: 10.1016/j.virol.2024.110284
Junyu Tang, Yu Fan Hung, Dongwan Yoo
Arteriviruses in the Nidovirales order are single-stranded positive-sense RNA viruses infecting mammals. Arteriviruses are recognized for causing various clinical diseases, ranging from asymptomatic infections to severe conditions like respiratory syndromes and viral hemorrhagic fever. Notably, arteriviruses exhibit a high frequency of RNA recombination, and their robust recombination rates are a crucial factor in recurrent outbreaks. The recombination events also shape the countermeasures employed by arteriviruses during virus-host co-evolution and confer specific evolutionary benefits to viruses, implicating a role as a selective advantage in viral adaptation. This review delves into the molecular basis of RNA recombination in arteriviruses, the bioinformatics tools and methodologies used to visualize evolutionary relationships, and the identification of recombination breakpoints. Significant recombination events are highlighted for PRRSV and other arteriviruses, illustrating the profound implications of recombination for viral evolution and pathogenesis. Recombination between field viruses and between field viruses and vaccine strains can generate new variants with altered antigenic profiles and virulence, leading to diagnostic failure, severe clinical outcomes, and reduced vaccine efficacy. Despite the advances, further research is needed to understand recombination rates and hotspots, as well as to develop potential antiviral strategies and diagnostic approaches for arteriviruses.
{"title":"Genomic RNA recombination of porcine reproductive and respiratory syndrome virus and other arteriviruses","authors":"Junyu Tang, Yu Fan Hung, Dongwan Yoo","doi":"10.1016/j.virol.2024.110284","DOIUrl":"10.1016/j.virol.2024.110284","url":null,"abstract":"<div><div>Arteriviruses in the <em>Nidovirales</em> order are single-stranded positive-sense RNA viruses infecting mammals. Arteriviruses are recognized for causing various clinical diseases, ranging from asymptomatic infections to severe conditions like respiratory syndromes and viral hemorrhagic fever. Notably, arteriviruses exhibit a high frequency of RNA recombination, and their robust recombination rates are a crucial factor in recurrent outbreaks. The recombination events also shape the countermeasures employed by arteriviruses during virus-host co-evolution and confer specific evolutionary benefits to viruses, implicating a role as a selective advantage in viral adaptation. This review delves into the molecular basis of RNA recombination in arteriviruses, the bioinformatics tools and methodologies used to visualize evolutionary relationships, and the identification of recombination breakpoints. Significant recombination events are highlighted for PRRSV and other arteriviruses, illustrating the profound implications of recombination for viral evolution and pathogenesis. Recombination between field viruses and between field viruses and vaccine strains can generate new variants with altered antigenic profiles and virulence, leading to diagnostic failure, severe clinical outcomes, and reduced vaccine efficacy. Despite the advances, further research is needed to understand recombination rates and hotspots, as well as to develop potential antiviral strategies and diagnostic approaches for arteriviruses.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110284"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635389","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 : 2024-10-31DOI: 10.1016/j.virol.2024.110282
Mengfang Yang , Yuzhou Jiao , Yuanyuan Yan , Zhen Fu , Lisha Li , Zirui Liu , Lingying Fang , Xiaoshuai Hu , Benyuan Wu , Yuejun Shi , Mengxia Li , Zhou Shen , Guiqing Peng
Vaccine efficacy relies not only on antigens but also on immunomodulatory agents/adjuvants that are often used to stimulate the immune system and enhance the immune response. However, current immunomodulatory agents are used to increase the immune response induced by viral or bacterial inactivated vaccine antigens, bacterial toxoids or polysaccharides but not attenuated live viruses. Based on the immunomodulatory functions of G-CSF and the characteristics of feline herpesvirus-1 (FHV-1) as an expression vector, a recombinant virus expressing feline G-CSF (WH2020-ΔTK/gI/gE-G-CSF) was constructed. The growth dynamics of WH2020-ΔTK/gI/gE-G-CSF were similar to those of WH2020-ΔTK/gI/gE. Compared with kittens vaccinated with WH2020 Δ TK/gI/gE, felines inoculated with WH2020 ΔTK/gI/gE-G-CSF produced more neutralizing antibodies and neutrophils, further alleviating clinical symptoms after FHV-1 infection. Taken together, our results revealed the potential of G-CSF as an ideal immune potentiator that can augment immune responses to FHV-1 and even other attenuated live vaccines.
{"title":"Recombinant feline herpesvirus-1 (FHV-1) expressing granulocyte colony-stimulating factor (G-CSF) exhibits enhanced protective efficacy in felines","authors":"Mengfang Yang , Yuzhou Jiao , Yuanyuan Yan , Zhen Fu , Lisha Li , Zirui Liu , Lingying Fang , Xiaoshuai Hu , Benyuan Wu , Yuejun Shi , Mengxia Li , Zhou Shen , Guiqing Peng","doi":"10.1016/j.virol.2024.110282","DOIUrl":"10.1016/j.virol.2024.110282","url":null,"abstract":"<div><div>Vaccine efficacy relies not only on antigens but also on immunomodulatory agents/adjuvants that are often used to stimulate the immune system and enhance the immune response. However, current immunomodulatory agents are used to increase the immune response induced by viral or bacterial inactivated vaccine antigens, bacterial toxoids or polysaccharides but not attenuated live viruses. Based on the immunomodulatory functions of G-CSF and the characteristics of feline herpesvirus-1 (FHV-1) as an expression vector, a recombinant virus expressing feline G-CSF (WH2020-ΔTK/gI/gE-G-CSF) was constructed. The growth dynamics of WH2020-ΔTK/gI/gE-G-CSF were similar to those of WH2020-ΔTK/gI/gE. Compared with kittens vaccinated with WH2020 Δ TK/gI/gE, felines inoculated with WH2020 ΔTK/gI/gE-G-CSF produced more neutralizing antibodies and neutrophils, further alleviating clinical symptoms after FHV-1 infection. Taken together, our results revealed the potential of G-CSF as an ideal immune potentiator that can augment immune responses to FHV-1 and even other attenuated live vaccines.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110282"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635396","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 : 2024-10-31DOI: 10.1016/j.virol.2024.110283
Fayu Yang , Yuxi Yang , Xiaoyun Li , Saba Aliyari , Guoliang Zhu , Zixiang Zhu , Haixue Zheng , Shilei Zhang
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a hemorrhagic illness with high fatality rates in domestic pigs that has resulted in a substantial socio-economic loss and threatens the global pork industry. Very few safe and efficient vaccines or compounds against ASF are commercially available, thus developing new antiviral strategies is urgently required. Targeted protein degradation (TPD) has emerged as one of the most innovative strategies for drug discovery. In this study, we generate Nanobody-based TRIM-aways specifically binding with and targeting ASFV-encoded structural proteins p30, p54, and p72 for degradation. Furthermore, nanobody-based trim-aways exhibit robust viral structural protein degradation capabilities in ASFV-infected iPAM and MA104 cells through both proteasomal and lysosomal pathways, concurrently demonstrating potent anti-ASFV activity with less viral production. Our study highlights the Nanobody-based TRIM-away targeting viral protein degradation as a potential candidate for the development of a novel antiviral strategy against ASF.
{"title":"A Nanobody-based TRIM-away targets the intracellular protein degradation of African swine fever virus","authors":"Fayu Yang , Yuxi Yang , Xiaoyun Li , Saba Aliyari , Guoliang Zhu , Zixiang Zhu , Haixue Zheng , Shilei Zhang","doi":"10.1016/j.virol.2024.110283","DOIUrl":"10.1016/j.virol.2024.110283","url":null,"abstract":"<div><div>African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a hemorrhagic illness with high fatality rates in domestic pigs that has resulted in a substantial socio-economic loss and threatens the global pork industry. Very few safe and efficient vaccines or compounds against ASF are commercially available, thus developing new antiviral strategies is urgently required. Targeted protein degradation (TPD) has emerged as one of the most innovative strategies for drug discovery. In this study, we generate Nanobody-based TRIM-aways specifically binding with and targeting ASFV-encoded structural proteins p30, p54, and p72 for degradation. Furthermore, nanobody-based trim-aways exhibit robust viral structural protein degradation capabilities in ASFV-infected iPAM and MA104 cells through both proteasomal and lysosomal pathways, concurrently demonstrating potent anti-ASFV activity with less viral production. Our study highlights the Nanobody-based TRIM-away targeting viral protein degradation as a potential candidate for the development of a novel antiviral strategy against ASF.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"600 ","pages":"Article 110283"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569190","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}
Coxsackievirus A6 (CVA6) is a primary pathogen associated with hand, foot, and mouth disease (HFMD) and is typified by fever, rashes or herpetic lesions at distinct locations. Although HFMD patients exhibit mild symptoms, a subset of patients may develop severe complications, such as viral encephalitis, myocarditis, pneumonia, and neurological disorders. However, in addition to rodent models, such as the CVA6-infected mouse model, no definitive nonhuman primate animal model or related research or analysis tool is available, which makes the development of suitable nonhuman primate animal models particularly crucial. In this study, 3- to 4-month-old rhesus monkeys were infected via the respiratory or digestive tract, and the pathogenic, pathological, and immunological alterations following CVA6 infection were investigated. The results revealed that the infected rhesus monkeys exhibited symptoms similar to those of patients, including signs of HFMD, blood cell changes, viremia, viral excretion, and inflammatory reactions during the acute phase (1–11 days). Pathological observations revealed inflammatory reactions in the intestinal and lymph node tissues. Notably, the acute symptoms gradually waned in the recovery phase (12–120 days), and a high level of neutralizing antibodies was sustained. Intriguingly, no significant disparity was observed between the infections initiated via the respiratory or digestive tract in terms of clinical symptoms, hemogram results or virus shedding. Overall, this study yielded a comprehensive dataset regarding the physiological, pathological, and immunological outcomes of CVA6 infection in a primate host, enhancing our comprehension of the mechanism of CVA6 infection and providing essential data for related vaccine and drug development.
{"title":"Establishment of a rhesus macaque model for coxsackievirus A6 infection: Pilot study to evaluate infection initiated through the respiratory or digestive track","authors":"Suqin Duan , Jinghan Hou , Yanyan Li, Ming Zhang, Yuan Zhao, Weihua Jin, Mingxue Li, Wenting Sun, Hongjie Xu, Quan Liu, Lixiong Chen, Zijun Deng, Fengmei Yang, Shaohui Ma, Zhanlong He","doi":"10.1016/j.virol.2024.110268","DOIUrl":"10.1016/j.virol.2024.110268","url":null,"abstract":"<div><div>Coxsackievirus A6 (CVA6) is a primary pathogen associated with hand, foot, and mouth disease (HFMD) and is typified by fever, rashes or herpetic lesions at distinct locations. Although HFMD patients exhibit mild symptoms, a subset of patients may develop severe complications, such as viral encephalitis, myocarditis, pneumonia, and neurological disorders. However, in addition to rodent models, such as the CVA6-infected mouse model, no definitive nonhuman primate animal model or related research or analysis tool is available, which makes the development of suitable nonhuman primate animal models particularly crucial. In this study, 3- to 4-month-old rhesus monkeys were infected via the respiratory or digestive tract, and the pathogenic, pathological, and immunological alterations following CVA6 infection were investigated. The results revealed that the infected rhesus monkeys exhibited symptoms similar to those of patients, including signs of HFMD, blood cell changes, viremia, viral excretion, and inflammatory reactions during the acute phase (1–11 days). Pathological observations revealed inflammatory reactions in the intestinal and lymph node tissues. Notably, the acute symptoms gradually waned in the recovery phase (12–120 days), and a high level of neutralizing antibodies was sustained. Intriguingly, no significant disparity was observed between the infections initiated via the respiratory or digestive tract in terms of clinical symptoms, hemogram results or virus shedding. Overall, this study yielded a comprehensive dataset regarding the physiological, pathological, and immunological outcomes of CVA6 infection in a primate host, enhancing our comprehension of the mechanism of CVA6 infection and providing essential data for related vaccine and drug development.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"601 ","pages":"Article 110268"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635387","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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