Journal of Virology最新文献

{"title":"Class IIa histone deacetylase (HDAC) inhibitor TMP269 suppresses lumpy skin disease virus replication by regulating host lysophosphatidic acid metabolism.","authors":"Pengyuan Cheng, Xiangwei Wang, Shasha Wang, Shanhui Ren, Zhengji Liang, Ke Guo, Min Qu, Xuelian Meng, Yongxi Dou, Xiangping Yin, Yuefeng Sun","doi":"10.1128/jvi.01827-24","DOIUrl":"10.1128/jvi.01827-24","url":null,"abstract":"<p><p>Lumpy skin disease virus (LSDV) infection poses a significant threat to global cattle farming. Currently, effective therapeutic agents are lacking. TMP269, a small molecule inhibitor of class IIa histone deacetylase inhibitor, plays a vital role in cancer therapy. In this study, we demonstrated that TMP269 treatment inhibits the early-stage replication of LSDV in a dose-dependent manner. RNA sequencing data revealed that metabolism-related signaling pathways were significantly enriched after LSDV infection. Furthermore, untargeted metabolomics analysis revealed that lysophosphatidic acid (LPA), a key metabolite of the glycerophospholipid pathway, was upregulated following LSDV infection and downregulated after TMP269 treatment. In addition, exogenous LPA promotes LSDV replication by activating the mitogen-activated protein kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway and suppressing the host's innate immune response. Furthermore, treatment with the LPA receptor inhibitor Ki16425 suppressed LSDV replication and promoted the host's innate immune response. These findings suggest that LSDV infection can induce LPA expression and aid viral activation of the MEK/ERK signaling pathway and escape of the host's innate immune response, whereas TMP269 treatment can inhibit LPA production and limit its promotion of LSDV replication. These data identified the antiviral mechanism of TMP269 and a novel mechanism by which LSDV inhibits host innate immune responses, providing insights into the development of new preventive or therapeutic strategies targeting altered metabolic pathways.IMPORTANCELumpy skin disease virus (LSDV) poses a significant threat to global cattle farming. Owing to insufficient research on LSDV infection, pathogenesis, and immune escape mechanisms, prevention and control methods against LSDV infection are lacking. Here, we found that TMP269, a class IIa histone deacetylase inhibitor, significantly inhibited LSDV replication. We further demonstrated that TMP269 altered LSDV infection-induced host glycerophospholipid metabolism. In addition, TMP269 decreased the accumulation of lysophosphatidic acid (LPA), a key metabolite in glycerophospholipid metabolism, induced by LSDV infection, and exogenous LPA-promoted LSDV replication by activating the mitogen-activated protein kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway and suppressing the host innate immune response. Our findings identified the antiviral mechanism of TMP269 and a novel mechanism by which LSDV manipulates host signaling pathways to promote its replication, offering insights into the development of novel antiviral agents against LSDV infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0182724"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNASEK interacting with PEDV structural proteins facilitates virus entry via clathrin-mediated endocytosis.","authors":"Wenzhen Qin, Ning Kong, Shengsong Xie, Hailong Liu, Xinyu Yang, Yahe Wang, Xinyu Cao, Yuchang Liu, Jiarui Wang, He Sun, Wu Tong, Hai Yu, Hao Zheng, Wen Zhang, Guangzhi Tong, Tongling Shan","doi":"10.1128/jvi.01760-24","DOIUrl":"10.1128/jvi.01760-24","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV), as a type of Alphacoronavirus causing acute diarrhea and high death rate among sucking piglets, poses great financial damage to the swine industry. Nevertheless, the molecular mechanism whereby PEDV enters host cells is unclear, limiting the development of PED vaccines and anti-PEDV agents. The present study found that the host protein ribonuclease kappa (RNASEK) was regulated by USF2, a transcription factor, and facilitated the PEDV replication. RNASEK was identified as a novel binding partner of PEDV, which interacted with a spike (S), envelope (E), and membrane (M) proteins on PEDV virion surfaces to increase the uptake not for attachment of PEDV virions. PEDV enters cells through the endocytosis pathways. RNASEK knockdown or RNASEK knockout assay revealed that through clathrin-mediated endocytosis (CME), RNASEK promoted the internalization of PEDV virions. Clathrin and the adaptor protein EPS15 only interacted with PEDV E protein, demonstrating that the RNASEK could target more virions through interaction with PEDV S, E, and M proteins to clathrin and EPS15 proteins rather than merely interacting with PEDV E protein to mediate the PEDV entry through CME. Moreover, our findings suggest that RNASEK, a newly identified host-entry factor, facilitates PEDV internalization by increasing the interaction of PEDV virions and EPS15-clathrin complex and may also provide a potential target for anti-PEDV therapies.IMPORTANCEPEDV is the causative pathogen of porcine diarrhea, which is a highly infectious acute intestinal condition, that poses significant economic damage to the swine industry. However, the existing PED vaccines fail to provide adequate protection for piglets against PEDV infection. Although PEDV replication in cells has been widely described, the mechanisms beneath PEDV entry of the host cells are incompletely understood. In this study, we showed that RNASEK, regulated by the transcription factor USF2, is a new host factor increasing PEDV infection in LLC-PK1 cells. RNASEK can bind to multiple structural proteins of PEDV (S, E, and M proteins), therefore increasing the interaction between PEDV virions, clathrin, and EPS15 to promote PEDV virion entry. Apart from unraveling the entry mechanisms of PEDV, our findings also contributed to facilitating the development of anti-PEDV agents and PED vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0176024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of M2 proteins of pneumoviruses in transcription regulation, prevention of hypermutation, and activation of the type I interferon pathway.","authors":"Pau Ribó-Molina, Kevin Groen, Balasubramanian Susma, Stefan van Nieuwkoop, Mathis Funk, Ron A M Fouchier, Bernadette G van den Hoogen","doi":"10.1128/jvi.01243-24","DOIUrl":"10.1128/jvi.01243-24","url":null,"abstract":"<p><p>Human metapneumovirus (HMPV) is an important causative agent of respiratory tract disease. Fundamental knowledge of the interaction between HMPV and the innate immune system could lead to the design of novel antiviral therapies. Previously, we demonstrated that HMPV M2-2 deletion mutants had hypermutated genomes and contained defective interfering particles (DIs), which are potent inducers of the IFN response. Here, we investigated the role of the HMPV M2-2 protein as IFN antagonist using chimeric HMPV expressing M2 proteins of other pneumoviruses: respiratory syncytial virus (RSV) and avian metapneumovirus type C (AMPV/C). Chimeric HMPVs expressing the M2 proteins of RSV or AMPV/C were attenuated in HEp-2 cells but did not activate the IFN response, and their genomes were not hypermutated. In contrast, chimeric HMPVs expressing the M2-2 proteins of RSV and AMPV/C, in combination with HMPV M2-1, did activate the IFN response, and their genomes were hypermutated. Investigation of the role of the pneumovirus M2 proteins in transcription regulation demonstrated that the M2-2 protein, only in concerted action with autologous M2-1 protein, acted as a transcription elongation factor. As a second approach, chimeric RSV in which the IFN antagonists NS1 and NS2 were replaced by the HMPV M2-2 gene failed to suppress an IFN response, indicating that the HMPV M2-2 protein is not a potent IFN antagonist. These data indicate that expression of autologous M2-1 and M2-2 proteins is important for the fidelity of the RNA-dependent RNA polymerase, necessary to prevent the accumulation of mutations, and possibly DIs, thereby preventing activation of the IFN responses.IMPORTANCEThe M2-2 protein of human metapneumovirus is suggested to function as a type I interferon antagonist, a function so far not assigned to the M2 proteins of other pneumoviruses. Although M2-2 deletion mutants of HMPV activate the type I interferon pathway, these mutants have hypermutated genomes and contain defective interfering RNAs, known to activate the interferon pathway. Here, we show that the M2-2 protein, in concerted action with autologous M2-1 protein, acts as a transcription elongation factor, which could explain the accumulation of DIs in M2-2 deletion mutants. Additionally, chimeric RSV in which the IFN antagonists NS1 and NS2 were replaced by the HMPV M2-2 gene failed to suppress an IFN response. These data indicate that expression of autologous M2-1 and M2-2 proteins is required for the fidelity of the RNA-dependent RNA polymerase to prevent genome hypermutation and activation of the type I IFN pathway.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0124324"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A splice donor in <i>E6</i> influences keratinocyte immortalization by beta-HPV49.","authors":"Tina M Rehm, Thomas Iftner, Frank Stubenrauch","doi":"10.1128/jvi.01640-24","DOIUrl":"10.1128/jvi.01640-24","url":null,"abstract":"<p><p>Human papillomaviruses (HPV) from the genus beta have been implicated in the development of cutaneous squamous cell cancer in <i>epidermodysplasia verruciformis</i> and organ transplant patients. In contrast to alpha-high-risk HPV, which cause ano-genital and oropharyngeal cancers, beta-HPV replication is not well understood. The beta-HPV49 transcriptome was analyzed by RNA sequencing using stable keratinocyte cell lines maintaining high levels of extrachromosomally replicating E8- genomes, which can be established due to a lack of the viral E8^E2 repressor protein. This analysis indicated the presence of four transcription start sites, two polyadenylation signals, and splice donor (SD) and acceptor sites consistent with the conserved gene expression patterns of animal and human PV. Surprisingly, a novel SD in the <i>E6</i> oncogene (SD217) was identified resembling the SD in <i>E6</i> of carcinogenic alpha-HPV. Mutation of SD217 enhanced E6 protein expression but had no influence on the growth of keratinocytes transduced with retroviral HPV49 E6 and E7 expression vectors. Inactivation of SD217 in the context of the HPV49 wild-type genome did not enable immortalization and prevented immortalization in the context of the E8- genome. The analysis of SD217 mutant genomes revealed a strong down-regulation of SD217 usage, but only weak effects on other viral transcripts. This suggests that SD217 does not contribute to immortalization by modulating viral gene expression. Usage of SD217 is increased in immortalized E8- cell lines compared with transiently transfected cells, which may indicate that long-term extrachromosomal maintenance requires reduced E6 protein levels.IMPORTANCEHigh-risk (hr) human papillomaviruses (HPV) from the genus alpha cause ano-genital and oropharyngeal cancers, whereas beta-HPV have been implicated to cause skin cancer in <i>epidermodysplasia verruciformis</i> and organ transplant patients. In contrast to alpha hr-HPV, the replication cycle of beta-HPV is not very well understood. Transcriptional profiling of beta-HPV49 by RNA sequencing reveals transcription start sites and splice sites conserved among HPV. Surprisingly, a splice donor site in the <i>E6</i> oncogene (SD217), previously only described for hr-HPV, was identified that controls E6 oncoprotein levels and is required for immortalization of keratinocytes by the HPV49 genome.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0164024"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Kajaste-Rudnitski et al., \"TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements\".","authors":"Anna Kajaste-Rudnitski, Sara S Marelli, Cinzia Pultrone, Thomas Pertel, Pradeep D Uchil, Nadir Mechti, Walther Mothes, Guido Poli, Jeremy Luban, Elisa Vicenzi","doi":"10.1128/jvi.02071-24","DOIUrl":"10.1128/jvi.02071-24","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0207124"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection.","authors":"Carolyn Bomidi, Faith M Sawyer, Noah Shroyer, Margaret Conner, Mary K Estes, Sarah E Blutt","doi":"10.1128/jvi.01507-24","DOIUrl":"10.1128/jvi.01507-24","url":null,"abstract":"<p><p>Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, based on lack of shedding virus, despite the highly infectious nature of RV. This response was directly proportional to the extent of secretory cell deletion, with infection predominantly occurring in areas containing intact secretory cells. RV infection of <i>Muc2</i> knockout mice recapitulated the secretory cell deletion phenotype, indicating that goblet cell loss is responsible for attenuated infection. Transcriptome analysis of Atoh1cKO intestine via single-cell RNA sequencing revealed downregulation of MHC II molecules specifically in tip enterocytes, and MHC II^-/- mice were likewise resistant to RV infection. These data suggest a previously unknown role for both MUC2 and MHC II expression in susceptibility to RV infection.IMPORTANCERotavirus (RV) is a highly contagious pathogen that primarily infects mature intestinal enterocytes. Murine rotavirus readily infects infant and adult mice, enabling evaluation of RV infection and immunity. We report that mice lacking secretory cells are one of the few genetically modified mouse lines not susceptible to murine rotavirus. Further investigation revealed loss of mucin 2 (MUC2) expression or major histocompatibility complex II (MCH II) expression recapitulated this rare resistance to rotavirus infection, suggesting a previously unrecognized link between secretory cell products and major histocompatibility complex II expression. Furthermore, these mouse models provide a platform to investigate rotavirus pathogenesis.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0150724"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential role of <i>cis</i>-encoded mature NS3 in the genome packaging of classical swine fever virus.","authors":"Benjamin Lamp, Sandra Barth, Carina Reuscher, Sebastian Affeldt, Angelika Cechini, Anette Netsch, Irmin Lobedank, Till Rümenapf","doi":"10.1128/jvi.01209-24","DOIUrl":"10.1128/jvi.01209-24","url":null,"abstract":"<p><p>Classical swine fever virus (CSFV) is a member of the genus <i>Pestivirus</i> within the family <i>Flaviviridae</i>. The enveloped particles contain a plus-stranded RNA genome encoding a single large polyprotein. The processing of this polyprotein undergoes dynamic changes throughout the infection cycle. The release of mature NS3 from the polyprotein is mediated and regulated by the NS2 autoprotease and a cellular co-factor, restricting efficient cleavage to the early phases of infection. NS3 is a multifunctional viral enzyme exhibiting helicase, NTPase, and protease activities pivotal for viral replication. Hence, the release of mature NS3 fuels replication, whereas unprocessed NS2-3 precursors are vital for progeny virus production in later phases of infection. Thus far, no packaging signals have been identified for pestivirus RNA. To explore the prerequisites for particle assembly, <i>trans</i>-packaging experiments were conducted using CSFV subgenomes and coreless CSFV strains. Intriguingly, we discovered a significant role of mature NS3 in genome packaging, effective only when the protein is encoded by the RNA molecule itself. This finding was reinforced by employing artificially engineered CSFV strains with duplicated NS3 genes, separating uncleavable NS2-3 precursors from mature NS3 molecules. The model for NS2-3/NS3 functions in genome packaging of pestiviruses appears to be much more complicated than anticipated, involving distinct functions of the mature NS3 and its precursor molecule NS2-3. Moreover, the reliance of genome packaging on <i>cis</i>-encoded NS3 may act as a downstream quality control mechanism, averting the packaging of defective genomes and coordinating the encapsidation of RNA molecules before membrane acquisition.</p><p><strong>Importance: </strong>Pestiviruses are economically significant pathogens in livestock. Although genome organization and non-structural protein functions resemble those of other <i>Flaviviridae</i> genera, distinct differences can be observed. Previous studies showed that coreless CSFV strains can produce coreless virions mediated by single compensatory mutations in NS3. In this study, we could show that only RNA molecules encoding these mutations in the mature NS3 are packaged in the absence of the core protein. Unlike this selectivity, a pool of structural proteins in the host cell was readily available for packaging all CSFV genomes. Similarly, the NS2-3-4A precursor molecules required for packaging could also be provided in <i>trans</i>. Consequently, genome packaging in pestiviruses is governed by <i>cis</i>-encoded mature NS3. Reliance on <i>cis</i>-acting proteins restricts the acceptance of defective genomes and establishes packaging specificity regardless of RNA sequence-specific packaging signals. Understanding the role of NS3 in pestiviral genome packaging might uncover new targets for antiviral therapies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0120924"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octahedral small virus-like particles of dengue virus type 2.","authors":"Adam Johnson, Martín Dodes Traian, Richard M Walsh, Simon Jenni, Stephen C Harrison","doi":"10.1128/jvi.01809-24","DOIUrl":"10.1128/jvi.01809-24","url":null,"abstract":"<p><p>Flavivirus envelope (E) and precursor M (prM) proteins, when ectopically expressed, assemble into empty, virus-like particles (VLPs). Cleavage of prM to M and loss of the pr fragment converts the VLPs from immature to mature particles, mimicking a similar maturation of authentic virions. Most of the VLPs obtained by prM-E expression are smaller than virions; early, low-resolution cryo-EM studies suggested a simple, 60-subunit, icosahedral organization. We describe here the cryo-EM structure of immature, small VLPs (smVLPs) from dengue virus type 2 and show that they have octahedral rather than icosahedral symmetry. The asymmetric unit of the octahedral particle is an asymmetric trimer of prM-E heterodimers, just as it is on icosahedral immature virions; the full, octahedrally symmetric particle thus has 24 such asymmetric trimers or 72 prM-E heterodimers in all. Cleavage of prM and release of pr generates ovoid, somewhat irregular, mature particles. Previous work has shown that mature smVLPs have fusion properties identical to those of virions, consistent with local, virion-like clustering of 36 E dimers on their surface. The cryo-EM structure and the properties of the smVLPs described here relate directly to ongoing efforts to use them as vaccine immunogens.</p><p><strong>Importance: </strong>Ectopic expression of flavivirus envelope (E) and precursor M (prM) proteins leads to the formation and secretion of empty, virus-like particles (VLPs). We show that a major class of VLPs, of smaller diameter than those of virion size (\"small VLPs\": smVLPs), are octahedrally symmetric particles. The known characteristics of immature virions (asymmetric trimers of prM-E heterodimers) allow us to understand the assembly of an octahedral (rather than icosahedral) surface lattice. Cleavage of prM and formation of mature, fusogenic smVLPs yield somewhat irregular, ovoid particles. These observations are directly relevant to proposals for using immunogenic but non-infectious VLPs as components of specific flavivirus vaccines.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0180924"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pasteurization temperatures effectively inactivate Rift Valley fever viruses in milk.","authors":"Aurélie Pédarrieu, Camille Piro-Megy, Jordan Quellec, Catherine Cêtre-Sossah","doi":"10.1128/jvi.02026-24","DOIUrl":"10.1128/jvi.02026-24","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0202624"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure of the T=13 capsid of infectious pancreatic necrosis virus (IPNV)-a salmonid birnavirus.","authors":"Anna Munke, Amr Ahmed Abdelrahim Gamil, Aase B Mikalsen, Han Wang, Øystein Evensen, Kenta Okamoto","doi":"10.1128/jvi.01454-24","DOIUrl":"10.1128/jvi.01454-24","url":null,"abstract":"<p><p>Birnaviruses infect a broad range of vertebrate hosts, including fish and birds, and cause substantial economic losses in the fishery and livestock industries. The infectious pancreatic necrosis virus (IPNV), an aquabirnavirus, specifically infects salmonids. While structures on T=1 subviral particles of the birnaviruses, including IPNV, have been studied, structural insights into the infectious T=13 particles have been limited to the infectious bursal disease virus (IBDV), an avibirnavirus. Determining the capsid structure of the T=13 particle of IPNV is crucial for advancing knowledge of its antigenicity, capsid assembly, and possible functional structures. Here, the capsid structure of the IPNV L5 strain has been determined at a resolution of 2.75 Å. The overall structure resembles the T=13 IBDV structure, with notable differences in the surface loops on the P domain of the VP2 capsid protein essential for antigenicity and virulence. Additionally, previously undescribed structural features have been identified, including the C-terminal regions of the VP2 subunits within the pentagonal assembly unit at each 5-fold axis, which interlock with adjacent VP2 subunits. This interlocking, together with class-averaged projections of triangular and pentagonal units, suggests that the pentagonal unit formation could be important for a correct T=13 particle assembly, preventing the formation of T=1 subviral particles. Furthermore, positively charged residues in obstructed capsid pores at each 5-fold axis are speculated to facilitate intraparticle genome synthesis of IPNV.IMPORTANCEAquabirnaviruses cause deadly infectious diseases in salmonid fish, posing significant challenges for both wild and farmed fish populations. The most prevalent aquabirnavirus worldwide is the infectious pancreatic necrosis virus, whose multifunctional capsid is critical to its infection, replication, and maturation. Previously, research has focused on the structure of the virus' non-infectious subviral capsid. In this study, however, the first structure of the large, infectious, and functional form of the capsid has been determined. This new capsid structure reveals functional motifs that were previously unclear in the non-infectious capsid. These motifs are believed to be essential for the virus' replication and particle assembly, making them promising targets for developing strategies to control virus proliferation.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0145424"},"PeriodicalIF":4.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}