Pub Date : 2025-02-01DOI: 10.1016/j.virol.2024.110366
Leandro R. Jones
Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense). Besides, evidence is reviewed that the virus can replicate and mutate in isolation at different anatomical compartments, which may imply that what we have learned from respiratory samples could be part of a broader picture.
{"title":"Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19","authors":"Leandro R. Jones","doi":"10.1016/j.virol.2024.110366","DOIUrl":"10.1016/j.virol.2024.110366","url":null,"abstract":"<div><div>Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense). Besides, evidence is reviewed that the virus can replicate and mutate in isolation at different anatomical compartments, which may imply that what we have learned from respiratory samples could be part of a broader picture.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110366"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901410","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110369
Chaoguang Gu , Yuqian Mo , Jiaqi Li , Xizhen Zhang , Siqi Xu , Meng Miao , Yanping Quan , Wei Yu
Late expression factor 3 (LEF3), a multifunctional single-stranded DNA binding protein encoded by baculoviruses, is indispensable for viral DNA replication and plays a pivotal role in viral infection. Our previous quantitative analysis of phosphorylomics revealed that the phosphorylation levels of two serine residues (S8 and S25) located in LEF3 nuclear localization sequence were significantly up-regulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection, but the underlying mechanism remained unknown. To investigate the impact of phosphorylation on BmNPV infection, site-direct mutagenesis was performed on LEF3 to obtain phosphorylated mimic (S/D) or dephosphorylated mimic (S/A) mutants. The results demonstrated that the viral replication and proliferation were inhibited by phosphorylation of S8 or S25. Furthermore, we found that the N-terminal 125 amino acids region was responsible for interacting with virus-encoded alkaline nuclease, but this interaction could be suppressed by the phosphorylation. Our findings indicated that phosphorylation may serve as an antiviral strategy for host.
{"title":"LEF3 phosphorylation attenuates the replication of Bombyx mori nucleopolyhedrovirus by suppressing its interaction with alkaline nuclease","authors":"Chaoguang Gu , Yuqian Mo , Jiaqi Li , Xizhen Zhang , Siqi Xu , Meng Miao , Yanping Quan , Wei Yu","doi":"10.1016/j.virol.2024.110369","DOIUrl":"10.1016/j.virol.2024.110369","url":null,"abstract":"<div><div>Late expression factor 3 (LEF3), a multifunctional single-stranded DNA binding protein encoded by baculoviruses, is indispensable for viral DNA replication and plays a pivotal role in viral infection. Our previous quantitative analysis of phosphorylomics revealed that the phosphorylation levels of two serine residues (S8 and S25) located in LEF3 nuclear localization sequence were significantly up-regulated after <em>Bombyx mori</em> nucleopolyhedrovirus (BmNPV) infection, but the underlying mechanism remained unknown. To investigate the impact of phosphorylation on BmNPV infection, site-direct mutagenesis was performed on LEF3 to obtain phosphorylated mimic (S/D) or dephosphorylated mimic (S/A) mutants. The results demonstrated that the viral replication and proliferation were inhibited by phosphorylation of S8 or S25. Furthermore, we found that the N-terminal 125 amino acids region was responsible for interacting with virus-encoded alkaline nuclease, but this interaction could be suppressed by the phosphorylation. Our findings indicated that phosphorylation may serve as an antiviral strategy for host.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110369"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904733","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110376
Angela Pearson, Amel Bouhamar
Members of the UL24 herpesvirus gene family are determinants of pathogenesis. The gene is widely conserved across the Orthoherpesviridae family, also commonly referred to as Herpesviridae. In this review, the impact of UL24 homologs on pathogenesis as studied with different model systems is presented, as well as mechanistic aspects related to the different roles of UL24 proteins in virus-host cell interactions. The targeting of UL24 for the development of therapeutic applications is also discussed.
{"title":"UL24 herpesvirus determinants of pathogenesis: Roles in virus-host interactions","authors":"Angela Pearson, Amel Bouhamar","doi":"10.1016/j.virol.2024.110376","DOIUrl":"10.1016/j.virol.2024.110376","url":null,"abstract":"<div><div>Members of the <em>UL24</em> herpesvirus gene family are determinants of pathogenesis. The gene is widely conserved across the <em>Orthoherpesviridae</em> family, also commonly referred to as <em>Herpesviridae</em>. In this review, the impact of <em>UL24</em> homologs on pathogenesis as studied with different model systems is presented, as well as mechanistic aspects related to the different roles of UL24 proteins in virus-host cell interactions. The targeting of <em>UL24</em> for the development of therapeutic applications is also discussed.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110376"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082925","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110319
Marko E. Popović , Vojin Tadić , Marta Popović
As of 26 April 2024, the International Committee on Taxonomy of Viruses has registered 14690 virus species. Of these, only several dozen have been chemically and thermodynamically characterized. Every virus species is characterized by a specific empirical formula and thermodynamic properties - enthalpy, entropy and Gibbs energy. These physical properties are used in a mechanistic model of virus-host interactions at the cell membrane and in the cytoplasm. This review article presents empirical formulas and Gibbs energies for all major variants of SARS-CoV-2. This article also reports and suggests a mechanistic model of evolutionary changes, with the example of time evolution of SARS-CoV-2 from 2019 to 2024.
{"title":"(R)evolution of Viruses: Introduction to biothermodynamics of viruses","authors":"Marko E. Popović , Vojin Tadić , Marta Popović","doi":"10.1016/j.virol.2024.110319","DOIUrl":"10.1016/j.virol.2024.110319","url":null,"abstract":"<div><div>As of 26 April 2024, the International Committee on Taxonomy of Viruses has registered 14690 virus species. Of these, only several dozen have been chemically and thermodynamically characterized. Every virus species is characterized by a specific empirical formula and thermodynamic properties - enthalpy, entropy and Gibbs energy. These physical properties are used in a mechanistic model of virus-host interactions at the cell membrane and in the cytoplasm. This review article presents empirical formulas and Gibbs energies for all major variants of SARS-CoV-2. This article also reports and suggests a mechanistic model of evolutionary changes, with the example of time evolution of SARS-CoV-2 from 2019 to 2024.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110319"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793103","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}
African swine fever virus (ASFV) poses a significant threat to the global swine industry and requires improved control strategies. Here, we developed a Differentiating Infected from Vaccinated Animals (DIVA) assay based on the MGF100-1L protein, which is absent in a cell-adapted ASFV strain lacking several multigene family (MGF) genes. We analyzed seven deleted genes, including MGF genes, from the right variable region of the ASFV genome against sera from convalescent pigs. MGF100-1L showed significant reactivity and was produced as a recombinant protein for use in an enzyme-linked immunosorbent assay (ELISA). The assay, with a cut-off value of 0.284, successfully differentiated between naive and infected pigs with 100% accuracy. More importantly, pigs infected with the cell-adapted ASFV showed no significant change in ELISA readouts after 27 days post-infection. However, when these pigs were subsequently challenged with wild-type virus, MGF100-1L reactivity increased significantly by 21 days post-challenge. This study demonstrates the potential of MGF100-1L as a DIVA marker for ASFV, which offers a promising tool to distinguish between infections with wild-type ASFV and those with cell-adapted variants lacking specific MGF genes, thereby improving ASFV surveillance and control strategies.
{"title":"Serologic differentiation between wild-type and cell-adapted African swine fever virus infections: A novel DIVA strategy using the MGF100-1L protein","authors":"Theeradej Thaweerattanasinp, Janya Saenboonrueng, Asawin Wanitchang, Kanjana Srisutthisamphan, Nathiphat Tanwattana, Ratchanont Viriyakitkosol, Challika Kaewborisuth, Anan Jongkaewwattana","doi":"10.1016/j.virol.2024.110349","DOIUrl":"10.1016/j.virol.2024.110349","url":null,"abstract":"<div><div>African swine fever virus (ASFV) poses a significant threat to the global swine industry and requires improved control strategies. Here, we developed a Differentiating Infected from Vaccinated Animals (DIVA) assay based on the MGF100-1L protein, which is absent in a cell-adapted ASFV strain lacking several multigene family (MGF) genes. We analyzed seven deleted genes, including MGF genes, from the right variable region of the ASFV genome against sera from convalescent pigs. MGF100-1L showed significant reactivity and was produced as a recombinant protein for use in an enzyme-linked immunosorbent assay (ELISA). The assay, with a cut-off value of 0.284, successfully differentiated between naive and infected pigs with 100% accuracy. More importantly, pigs infected with the cell-adapted ASFV showed no significant change in ELISA readouts after 27 days post-infection. However, when these pigs were subsequently challenged with wild-type virus, MGF100-1L reactivity increased significantly by 21 days post-challenge. This study demonstrates the potential of MGF100-1L as a DIVA marker for ASFV, which offers a promising tool to distinguish between infections with wild-type ASFV and those with cell-adapted variants lacking specific MGF genes, thereby improving ASFV surveillance and control strategies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110349"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831488","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110313
Abid Ullah Shah , Phillip Gauger , Maged Gomaa Hemida
BCoV new isolate was plaque purified, isolated, and propagated in vitro using MDBK and HRT-18. The full-length genome sequencing of this new BCoV isolate (31 Kbs) was drafted and deported in the GenBank. The genome organization is (5′-UTR-Gene-1-32kDa-HE-S-4.9 kDa-4.8 kDa-12.7 kDa-E-M-N-UTR-3′). Phylogenetic analysis based on the sequences of (the full-length genome, S, HE, and N) showed that the BCoV-13 clustered with other North American BCoV genotype I members. The sequence analysis shows several synonymous mutations among various domains of the S glycoprotein, especially the receptor binding domain. We found nine notable nucleotide deletions immediately downstream of the RNA binding domain of the nucleocapsid gene. Further gene function studies are encouraged to study the function of these mutations on the BCoV molecular pathogenesis and immune regulation. This research enhances our understanding of BCoV genomics and contributes to improved diagnostic and control measures for BCoV infections in cattle.
{"title":"Isolation and molecular characterization of an enteric isolate of the genotype-Ia bovine coronavirus with notable mutations in the receptor binding domain of the spike glycoprotein","authors":"Abid Ullah Shah , Phillip Gauger , Maged Gomaa Hemida","doi":"10.1016/j.virol.2024.110313","DOIUrl":"10.1016/j.virol.2024.110313","url":null,"abstract":"<div><div>BCoV new isolate was plaque purified, isolated, and propagated <em>in vitro</em> using MDBK and HRT-18. The full-length genome sequencing of this new BCoV isolate (31 Kbs) was drafted and deported in the GenBank. The genome organization is (5′-UTR-Gene-1-32kDa-HE-S-4.9 kDa-4.8 kDa-12.7 kDa-E-M-N-UTR-3′). Phylogenetic analysis based on the sequences of (the full-length genome, S, HE, and N) showed that the BCoV-13 clustered with other North American BCoV genotype I members. The sequence analysis shows several synonymous mutations among various domains of the S glycoprotein, especially the receptor binding domain. We found nine notable nucleotide deletions immediately downstream of the RNA binding domain of the nucleocapsid gene. Further gene function studies are encouraged to study the function of these mutations on the BCoV molecular pathogenesis and immune regulation. This research enhances our understanding of BCoV genomics and contributes to improved diagnostic and control measures for BCoV infections in cattle.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110313"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840719","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110363
Peter D. Nagy, Judit Pogany, Yuanrong Kang
Positive-strand (+)RNA viruses are major pathogens of humans, animals and plants. This review summarizes the complex interplay between the host autophagy pathway and Tomato bushy stunt virus (TBSV) replication. Recent discoveries with TBSV have revealed virus-driven exploitation of autophagy in multiple ways that contributes to the unique phospholipid composition of viral replication organellar (VROs) membranes. Viral replication protein-driven subversion of phagophore membranes, recruitment of ATG2 bulk lipid transfer protein to enrich phosphatidylethanolamine and phosphatidylserine in VROs, recruitment of VPS34 PI3K to produce PI(3)P; and ATG11-facilitated formation of stable viral membrane contact sites contributes to VRO membrane proliferation. Recruitment of autophagy core proteins to vir-NBR1 bodies within vir-condensates associated with VROs results in dampened antiviral degradation by autophagy. Overall, TBSV intricate interplay with the autophagy machinery highlights the importance of lipid dynamics in viral life cycles and points toward potential directions for therapeutic intervention.
{"title":"Novel exploitation of autophagy by tombusviruses","authors":"Peter D. Nagy, Judit Pogany, Yuanrong Kang","doi":"10.1016/j.virol.2024.110363","DOIUrl":"10.1016/j.virol.2024.110363","url":null,"abstract":"<div><div>Positive-strand (+)RNA viruses are major pathogens of humans, animals and plants. This review summarizes the complex interplay between the host autophagy pathway and <em>Tomato bushy stunt virus</em> (TBSV) replication. Recent discoveries with TBSV have revealed virus-driven exploitation of autophagy in multiple ways that contributes to the unique phospholipid composition of viral replication organellar (VROs) membranes. Viral replication protein-driven subversion of phagophore membranes, recruitment of ATG2 bulk lipid transfer protein to enrich phosphatidylethanolamine and phosphatidylserine in VROs, recruitment of VPS34 PI3K to produce PI(3)P; and ATG11-facilitated formation of stable viral membrane contact sites contributes to VRO membrane proliferation. Recruitment of autophagy core proteins to vir-NBR1 bodies within vir-condensates associated with VROs results in dampened antiviral degradation by autophagy. Overall, TBSV intricate interplay with the autophagy machinery highlights the importance of lipid dynamics in viral life cycles and points toward potential directions for therapeutic intervention.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110363"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873807","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110377
Satyanarayana Tatineni , Shaonpius Mondal , Stephen N. Wegulo , Gary L. Hein
Triticum mosaic virus (TriMV; Poacevirus tritici) is the founding member of the genus Poacevirus within the family Potyviridae. TriMV is one of the components of the wheat streak mosaic disease (WSMD) complex, an economically significant wheat disease in the Great Plains region of the USA. TriMV contains a single-stranded positive-sense RNA genome of 10,266 nts with an unusually long 5′-nontranslated region of 739 nts. TriMV is transmitted only by the Type-2 genotype of wheat curl mites (Aceria tosichella Keifer) and is mostly found as a co-infection with another wheat curl mite-transmitted wheat streak mosaic virus (WSMV). TriMV and WSMV synergistically interact in co-infected wheat with exacerbated disease symptoms. The development of an infectious cDNA clone and GFP or RFP-tagged stable expression vectors has advanced the functional genomics of TriMV, including virus-virus and virus-host interactions. NIa-Pro and CP, and P1 and NIa-Pro cistrons of TriMV are identified as elicitors of superinfection exclusion and determinants of synergistic interaction with WSMV, respectively. TriMV stably maintained P1 (1083 nts) plus NIa (1305 nts) cistrons of WSMV for more than 28 days postinoculation, suggesting that TriMV can be used as a stable gene expression vector in wheat. Because of the synchrony of the mites and viruses in this disease complex, primary management efforts should focus on the timing and presence of vector hosts. Importantly, an enhanced understanding of TriMV biology and its interactions with plants, mites, and WSMV will facilitate the development of effective tools to improve the sustainable management of the wheat-mite-virus complex.
{"title":"Triticum mosaic virus: An overview of biology, functional genomics, gene expression vector, and management strategies","authors":"Satyanarayana Tatineni , Shaonpius Mondal , Stephen N. Wegulo , Gary L. Hein","doi":"10.1016/j.virol.2024.110377","DOIUrl":"10.1016/j.virol.2024.110377","url":null,"abstract":"<div><div>Triticum mosaic virus (TriMV; <em>Poacevirus tritici</em>) is the founding member of the genus <em>Poacevirus</em> within the family <em>Potyviridae</em>. TriMV is one of the components of the wheat streak mosaic disease (WSMD) complex, an economically significant wheat disease in the Great Plains region of the USA. TriMV contains a single-stranded positive-sense RNA genome of 10,266 nts with an unusually long 5′-nontranslated region of 739 nts. TriMV is transmitted only by the Type-2 genotype of wheat curl mites (<em>Aceria tosichella</em> Keifer) and is mostly found as a co-infection with another wheat curl mite-transmitted wheat streak mosaic virus (WSMV). TriMV and WSMV synergistically interact in co-infected wheat with exacerbated disease symptoms. The development of an infectious cDNA clone and GFP or RFP-tagged stable expression vectors has advanced the functional genomics of TriMV, including virus-virus and virus-host interactions. NIa-Pro and CP, and P1 and NIa-Pro cistrons of TriMV are identified as elicitors of superinfection exclusion and determinants of synergistic interaction with WSMV, respectively. TriMV stably maintained P1 (1083 nts) plus NIa (1305 nts) cistrons of WSMV for more than 28 days postinoculation, suggesting that TriMV can be used as a stable gene expression vector in wheat. Because of the synchrony of the mites and viruses in this disease complex, primary management efforts should focus on the timing and presence of vector hosts. Importantly, an enhanced understanding of TriMV biology and its interactions with plants, mites, and WSMV will facilitate the development of effective tools to improve the sustainable management of the wheat-mite-virus complex.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110377"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901518","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}
Oz virus (OZV), a tick-borne, six-segmented negative-strand RNA virus in the genus Thogotovirus, caused a fatal human infection in Japan in 2023. To study viral RNA synthesis, we developed an OZV minigenome assay using mammalian cells. This revealed variations in promoter activities among the six genome segments. The "distal duplex," a double-stranded RNA structure beginning at the 11th nucleotide on the 5' end and the 10th on the 3' end, was found in all segments. A factor affecting promoter activity was the base pairing between the 12th nucleotide at the 5' end and the 11th at the 3' end, forming either G:C or A:U pairs. Disruption of this pairing caused a significant loss of promoter activity, emphasizing the importance of the distal duplex with at least six consecutive base pairs. Comparative analysis of genome terminal sequences suggests similar structural variations in the promoters of other species in Thogotovirus.
{"title":"Segment-specific promoter activity for RNA synthesis in the genome of Oz virus, genus Thogotovirus","authors":"Lipi Akter , Ryo Matsumura , Daisuke Kobayashi , Hiromichi Matsugo , Haruhiko Isawa , Yusuke Matsumoto","doi":"10.1016/j.virol.2025.110410","DOIUrl":"10.1016/j.virol.2025.110410","url":null,"abstract":"<div><div>Oz virus (OZV), a tick-borne, six-segmented negative-strand RNA virus in the genus <em>Thogotovirus</em>, caused a fatal human infection in Japan in 2023. To study viral RNA synthesis, we developed an OZV minigenome assay using mammalian cells. This revealed variations in promoter activities among the six genome segments. The \"distal duplex,\" a double-stranded RNA structure beginning at the 11th nucleotide on the 5' end and the 10th on the 3' end, was found in all segments. A factor affecting promoter activity was the base pairing between the 12th nucleotide at the 5' end and the 11th at the 3' end, forming either G:C or A:U pairs. Disruption of this pairing caused a significant loss of promoter activity, emphasizing the importance of the distal duplex with at least six consecutive base pairs. Comparative analysis of genome terminal sequences suggests similar structural variations in the promoters of other species in <em>Thogotovirus</em>.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110410"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019254","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 : 2025-02-01DOI: 10.1016/j.virol.2024.110320
Zsuzsa K. Szemere, Emmanuel Ijezie, Eain A. Murphy
The extracellular addition of the STING agonist, 2-3cGAMP, induces an antiviral state that inhibits HSV-1 replication in a cell type dependent manner via the transportation of the cyclic-dinucleotide through the folate antiporter SLC19A1. To establish a successful infection, herpes simplex virus-1 (HSV-1), a ubiquitous virus with high seropositivity in the human population, must undermine a multitude of host innate and intrinsic immune defense mechanisms, including key players of the STimulator of INterferon Genes (STING) pathway. Herein, we report that HSV-1 infection results in the reduction of SLC19A1 transcription, translation, and importantly, the rapid removal of SLC19A1 from the cell surface of infected cells. Our data indicate SLC19A1 functions as a newly identified antiviral mediator for extracellular 2′-3'cGAMP which is undermined by HSV-1 protein ICP27. This work presents novel and important findings about how HSV-1 manipulates the host's immune environment for viral replication and discovers details about an important antiviral mechanism.
{"title":"Herpes simplex virus-1 targets the 2′-3'cGAMP importer SLC19A1 as an antiviral countermeasure","authors":"Zsuzsa K. Szemere, Emmanuel Ijezie, Eain A. Murphy","doi":"10.1016/j.virol.2024.110320","DOIUrl":"10.1016/j.virol.2024.110320","url":null,"abstract":"<div><div>The extracellular addition of the STING agonist, 2-3cGAMP, induces an antiviral state that inhibits HSV-1 replication in a cell type dependent manner via the transportation of the cyclic-dinucleotide through the folate antiporter SLC19A1. To establish a successful infection, herpes simplex virus-1 (HSV-1), a ubiquitous virus with high seropositivity in the human population, must undermine a multitude of host innate and intrinsic immune defense mechanisms, including key players of the <u>ST</u>imulator of <u>IN</u>terferon <u>G</u>enes (STING) pathway. Herein, we report that HSV-1 infection results in the reduction of SLC19A1 transcription, translation, and importantly, the rapid removal of SLC19A1 from the cell surface of infected cells. Our data indicate SLC19A1 functions as a newly identified antiviral mediator for extracellular 2′-3'cGAMP which is undermined by HSV-1 protein ICP27. This work presents novel and important findings about how HSV-1 manipulates the host's immune environment for viral replication and discovers details about an important antiviral mechanism.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"603 ","pages":"Article 110320"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788354","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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