Journal of Virology最新文献

{"title":"Influenza infection of the mammary gland.","authors":"Alyson A Kelvin, Pari H Baker, Sourish Ghosh, Stacey Schultz-Cherry, Stephanie N Langel","doi":"10.1128/jvi.01940-24","DOIUrl":"10.1128/jvi.01940-24","url":null,"abstract":"<p><p>The mammary gland is an essential organ for milk production, providing essential immune and nutritional support to offspring and supplying dairy products for human consumption. In both humans and animals, the lactating mammary gland is susceptible to bacterial and viral infections, which can lead to mastitis and, in some cases, vertical transmission to offspring, with potential adverse effects on infant health. However, until recently, the role of respiratory viruses in mammary gland infection has been relatively understudied, particularly their ability to infect mammary epithelial cells and transmit through lactation. The recent emergence of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in dairy cattle has demonstrated the virus's capacity to replicate in the mammary gland, cause mastitis, and produce high viral loads in milk. This raises significant concerns about the potential for zoonotic transmission to humans and other animals in contact with infected dairy cows and unpasteurized milk. In this mini-review, we highlight key studies that demonstrate the replication of influenza and other viruses in the mammary gland, summarize recent findings from experimental and natural H5N1 clade 2.3.4.4b infections in dairy cows and small animal models, and discuss the broader One Health implications of the current H5N1 outbreak. We emphasize the urgent need for an interdisciplinary collaboration across sectors to mitigate the risks posed by influenza viruses with pandemic potential.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0194024"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821904","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":"Retinal transduction profiling of diverse AAV serotypes via intravitreal injection.","authors":"Tianlu Zhang, Fei Wang, Yang Wu, Jingjing Cao, Yin Shen","doi":"10.1128/jvi.00637-25","DOIUrl":"10.1128/jvi.00637-25","url":null,"abstract":"<p><p>Optimizing adeno-associated virus (AAV) capsid and dosing selection is critical for the clinical translation of retinal gene therapy. This study aims to provide a comprehensive reference by comparing the transduction efficiency, cellular tropisms, and temporal retinal expression patterns of various AAV serotypes for intravitreal retinal gene therapy. A series of AAV vectors were intravitreally injected into C57BL/6J mice. Retinal tissues were harvested 4 weeks post-injection to evaluate the transgene expression and cellular tropisms by immunostaining. Both ssAAV2.NN and scAAV2.NN vectors at a dose escalation were administered, with similar assessments conducted at 2 and 4 weeks post-injection. Additionally, the early-phase retinal transduction profiles of AAV vectors were detected at multiple time points within 12 weeks following administration. Stronger green fluorescent protein (GFP) fluorescence was observed in retinas intravitreally transduced with AAV2.NN, AAV2.GL, and AAV8 vectors, with AAV2.GL showing greater co-localization with GS⁺ Müller cells and axons. Compared to ssAAV2.NN, scAAV2.NN vectors resulted in higher GFP fluorescence, despite similar transfected cell percentages (except for its increased co-labeling with Calbindin⁺ horizontal cells). A dose-dependent level of GFP fluorescence was noted in scAAV2.NN vectors, with greater co-labeling with Rbpms⁺ retinal ganglion cells at high doses. Interestingly, GFP fluorescence was detectable as early as 3 days post-injection in both ssAAV2.NN and scAAV2.NN vectors, with no prominent differences in the intensity until day 7. AAV2.GL vectors achieved higher transgene expression and broader cellular transduction via the intravitreal route. scAAV2.NN vectors presented stronger transgene expression in a dose-dependent manner. The transgene expression from both ssAAV2.NN and scAAV2.NN vectors can be detected as early as 3 days post-injection. Our study provides key insights for early-stage monitoring and vector and dosage selection in future clinical application for intravitreal gene therapy.</p><p><strong>Importance: </strong>The retinal transduction efficiency and cellular tropisms of serial AAV serotypes, including AAV2, AAV2.7m8, AAV2.NN, AAV2.GL, AAV8, AAV11, and AAV.SPR, were simultaneously and unbiasedly quantified and compared following intravitreal injection. Transgene fluorescence was detectable in cells as early as 3 days post-injection in retinas intravitreally transduced with both ssAAV2.NN and scAAV2.NN vectors. The timeliness of the onset and level of transgene expression in retinas intravitreally transduced with ssAAV2.NN and scAAV2.NN vectors were characterized during the early phase post-injection. Differences in retinal transduction efficiency and cellular tropisms of scAAV2.NN vectors at varying doses via intravitreal injection are described.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0063725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821905","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":"Seneca Valley virus 3C protease targets TRIM32 for cleavage to antagonize its antiviral effects.","authors":"Jingjing Yang, Zijian Li, Ruiyi Ma, Shijie Xie, Dan Wang, Rong Quan, Jue Liu, Jiangwei Song","doi":"10.1128/jvi.00590-25","DOIUrl":"10.1128/jvi.00590-25","url":null,"abstract":"<p><p>The Seneca Valley virus (SVV), a newly emerged virus within the <i>Picornaviridae</i> family, causes porcine idiopathic vesicular disease, imposing substantial economic costs to the global pork industry. However, the molecular mechanisms underlying its pathogenesis remain poorly understood. In this study, we identified TRIM32 as a novel antiviral factor against SVV and found that SVV infection led to the cleavage and degradation of TRIM32. Knocking down TRIM32 increased viral replication, while overexpressing it reduced viral titers. Further study showed that TRIM32 restricts SVV replication by selectively targeting viral VP3 protein for ubiquitination and proteasomal degradation. To counteract this, SVV 3C protease (3Cpro) targets TRIM32 for cleavage at E332. This cleavage renders TRIM32 unable to inhibit SVV replication or block the degradation of VP3. Additionally, the cleaved TRIM32 products weaken E3 ubiquitin ligase activity and reduce activation of the type I interferon (IFN) pathway. Taken together, our results indicate that SVV 3C^pro-mediated cleavage of TRIM32 impairs its function in the ubiquitination and degradation of viral VP3 and type I IFN signaling. These findings offer novel insights into the strategies viruses use to evade the host's antiviral immune responses, thereby contributing to efficient viral replication.</p><p><strong>Importance: </strong>Seneca Valley virus (SVV) is an emerging pathogen that causes vesicular diseases in pigs, posing a significant threat to the global swine industry. Tripartite motif-containing protein (TRIM) family members are recognized as intrinsic antiviral effectors that provide a frontline shield against viruses prior to the transcription of interferon (IFN) and interferon-stimulated genes (ISGs). In this study, we uncovered the antiviral mechanism, which promotes the K48-linked ubiquitination of viral VP3 protein, leading to the degradation of VP3 via the proteasome pathway. SVV 3C^pro abolished the antiviral effects of TRIM32 by inducing its cleavage. The cleaved TRIM32 fragment attenuates its E3 ubiquitin ligase activity and weakens the activation of IFN signaling. Our results reveal a potential mechanism of viral immune evasion, which is crucial for understanding how SVV has evolved a novel strategy to evade the intrinsic cellular restrictions against viral infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0059025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821906","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":"Activation of the HPV16 late promoter by viral E2 and cellular BRD4 and ZC3H4 proteins.","authors":"Janis Renner, Karsten Boldt, Andreas Wieland, Adam Grundhoff, Thomas Guenther, Patrick Bluemke, Frank Stubenrauch, Thomas Iftner","doi":"10.1128/jvi.00762-25","DOIUrl":"10.1128/jvi.00762-25","url":null,"abstract":"<p><p>High-risk human papillomaviruses (HPV), particularly HPV16, are major causes of anogenital and oropharyngeal cancers. The HPV late promoter, P670 in the case of HPV16, is activated upon host cell differentiation and drives the expression of viral capsid proteins. While differentiation-specific host transcription factors have been implicated in regulating this promoter, the mechanism remains incompletely understood. HPV E2 proteins activate transcription by interacting with the host protein BRD4 (Bromodomain-containing protein 4). A biotin proximity ligation screen identified several novel E2 interactors, of which many overlap with the BRD4 interactome, suggesting BRD4 mediates a large fraction of these interactions. One such interactor, ZC3H4 (Zinc finger CCCH domain-containing protein 4), is known to restrict the expression of long non-coding RNAs, including enhancer and promoter upstream antisense RNAs (uaRNAs). E2 recruits ZC3H4 in a BRD4-dependent manner to specifically activate the P670 promoter in reporter assays. Supporting this, E2 and ZC3H4 co-localize in cells with high P670 activity. ZC3H4 is upregulated during differentiation, and its knockdown in differentiated HPV16- or HPV31-positive cells reduces late viral transcripts in an E2-BRD4-dependent manner. Interestingly, knockdown of ZC3H4 does not increase viral uaRNAs, suggesting that ZC3H4 does not enhance HPV late transcription by regulating viral antisense transcription.</p><p><strong>Importance: </strong>High-risk human papillomaviruses (HPVs), particularly HPV16, can cause anogenital and oropharyngeal cancers. HPV16 relies on the differentiation-dependent activation of its late promoter, P670, to produce capsid proteins. While host transcription factors contribute to this regulation, the mechanisms remain incompletely defined. Our findings reveal that the viral E2 protein collaborates with the host protein BRD4-a critical transcriptional regulator-to recruit other cellular partners, such as ZC3H4. Normally, ZC3H4 suppresses non-coding RNAs in cells, but HPV16 repurposes it via BRD4 to activate P670. This interaction intensifies in differentiated cells, where ZC3H4 levels rise, and disrupting ZC3H4 specifically blocks late viral gene expression without affecting antisense viral transcription. This highlights a unique, differentiation-dependent strategy HPV16 uses to hijack host machinery for its replication.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0076225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835482","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":"Deciphering the membrane topology of the pestiviral non-structural protein 4B (NS4B).","authors":"S Höppner, O Isken, N Tautz","doi":"10.1128/jvi.00825-25","DOIUrl":"10.1128/jvi.00825-25","url":null,"abstract":"<p><p>Pestiviruses like bovine viral diarrhea virus and other members of the family <i>Flaviviridae</i> form replication complexes consisting of viral non-structural and cellular proteins at rearranged intracellular membranes. Despite the pivotal roles of non-structural protein 4B (NS4B) throughout the pestiviral life cycle, little is known about how this protein exerts its multiple functions. It is assumed that pestiviral NS4B promotes replication complex assembly and virion morphogenesis by interacting with defined sets of viral and host proteins. The membrane topology of the protein dictates the availability of individual protein structures and interfaces for such interactions. Thus, the knowledge of the NS4B membrane topology is required for a detailed functional understanding of this protein. Therefore, we experimentally determined the membrane topology for NS4B <i>in cellulo</i> by using the substituted cysteine accessibility method (SCAM) in combination with computational secondary structure and transmembrane domain (TMD) predictions. Our model indicates the formation of two TMDs in the N-terminal region of NS4B (TMD2-3) followed by nine putative membrane-associated α-helices. Furthermore, a dual topology of the N-terminal amphipathic α-helix AH1 was detected by applying a Split-GFP assay, exposing similarities to hepatitis C virus NS4B. The translocation of AH1 across the membrane and the luminal orientation of the proposed loop connecting TMD2-3 was further confirmed by glycosylation acceptor site recognition analysis. Together, our model will assist further studies on the diverse functions of pestiviral NS4B throughout the viral life cycle.IMPORTANCEMembrane proteins are of special importance for positive-strand RNA viruses due to their replication at remodeled intracellular membranes. Moreover, the multi-functionality of these proteins can rely on alternative topologies. Studying their membrane topologies is challenging since protein purification can induce misfolding. Similarly, random insertions of large N-glycosylation acceptor sites may disturb transmembrane domains and thus the topology, while minimal glycosylation motifs (NXT/S) are often inefficiently glycosylated. Therefore, we used the SCAM assay utilizing single cysteine substitutions to analyze the membrane topology of BVDV-1 NS4B. A dual topology of the N-terminal region was demonstrated by a Split-GFP assay. Glycosylation acceptor site insertions at pre-analyzed positions further corroborated the model. In sum, BVDV-1 NS4B topology shows similarities but also remarkable differences to the NS4B membrane topologies of other <i>Flaviviridae</i> orthologues. This new information will allow further studies to clarify the molecular basis of the multi-functionality of this critical viral component.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0082525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835483","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":"GP2a I118 and GP4 D43 play critical roles in the attachment of PRRSV to the CD163 receptor: implications for anti-PRRSV infection targets.","authors":"Guoqing Liu, Xinyi Huang, Yongbo Yang, Meng Chen, Xiaoxiao Tian, Hao Song, Haojie Wang, Shujie Wang, Haiwei Wang, Xuehui Cai, Tongqing An","doi":"10.1128/jvi.00963-25","DOIUrl":"10.1128/jvi.00963-25","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global swine industry. Numerous modified live vaccines (MLVs) against PRRSV have been developed through the serial passage of wild-type parental strains in Marc-145 cells. However, the infectivity of these MLVs toward their primary target cell <i>in vivo</i>, porcine alveolar macrophage (PAM), is markedly reduced. The underlying mechanism for this decreased tropism remains unclear. In this study, we determined that the 118th residue in GP2a and the 43rd residue in GP4 play critical roles in determining viral tropism for PAM cells. Individual or combined mutations of GP2a-V118I and GP4-N43D significantly enhanced viral attachment to PAM cells. Furthermore, synthesized small peptides containing GP2a-I118 and GP4-D43 effectively blocked viral attachment to PAM cells in a dose-dependent manner, exhibiting broad-spectrum blocking effects against various PRRSV strains, including newly emerged NADC30- and NADC34-like PRRSVs. Coimmunoprecipitation (co-IP) results demonstrated that mutations or deletions at GP2a-V118 and GP4-N43 could significantly affect the binding affinity of GP2a and GP4 for the CD163 receptor, particularly the SRCR5 domain of CD163. Overall, for the first time, we identified two key residues associated with the reduced infectivity of PRRSV MLVs, which play essential roles in the attachment of PRRSV to the CD163 receptor. These findings provide novel insights into PRRSV tropism for PAM cells and reveal new targets for the development of peptide-based drugs or neutralizing antibodies against PRRSV infection.</p><p><strong>Importance: </strong>Currently, most modified live vaccines (MLVs) against animal diseases are derived from serial passages of parental virulent viruses in heterologous animal cells. This process enhances viral adaptation to heterologous cells while significantly reducing viral infectivity to host animal cells, thereby attenuating virulence in hosts. However, the mechanisms underlying the changes in tropism of many MLVs remain largely unknown. In this study, we identified and confirmed two key residues associated with changes in tropism. Importantly, we demonstrated that small peptides can block viral binding to receptors. These findings not only provide potential targets for the development of antiviral drugs or neutralizing antibodies but also offer valuable references for studying tropism changes in other viruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0096325"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873810","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":"E2-based mRNA vaccine encapsulated in lipid nanoparticles protects pigs against classical swine fever virus.","authors":"Jingyi Liu, Yingju Xia, Chuanwen Tian, Ziyu Chen, Weiqiang Guo, Yingnan Liu, Jing Wen, Zhenhua Xie, Jinzhong Lin, Jiaxin Li, Hongjun Chen, Yebing Liu","doi":"10.1128/jvi.00978-25","DOIUrl":"10.1128/jvi.00978-25","url":null,"abstract":"<p><p>Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), remains a significant threat to the global pig industry. Recent advances in mRNA vaccines offered a promising platform for combating CSFV. In this study, we designed and evaluated three lipid nanoparticle (LNP)-encapsulated mRNA vaccine candidates encoding the ectodomain of E2 glycoprotein (E2_EX), E2_EX fused with the transmembrane (TM) region of the PEDV S protein (E2tm), and E2_EX fused with the TM region of the influenza virus HA protein (E2tm-HA). Among these, the E2tm mRNA vaccine induced the most robust antibody responses in pigs. Immunization of piglets with the E2tm mRNA vaccine showed that its immunogenicity was not impaired by maternal antibodies. Comparative analysis of pseudouridine (Ψ)-modified (^ΨE2tm) and unmodified (E2tm) mRNA vaccines revealed that E2tm induced significantly higher antibodies titers than ^ΨE2tm. All vaccinated pigs survived the CSFV challenge, with the 150 µg E2tm dose providing optimal protection, effectively suppressing viremia and preventing viral dissemination to tissues while also resulting in undetectable viral RNA in swab samples. Our findings provide a promising novel mRNA vaccine that could be used as an alternative vaccination strategy against CSFV infection.</p><p><strong>Importance: </strong>Classical swine fever virus (CSFV) remains a significant threat to the global pig industry. While live attenuated and subunit vaccines are currently in use, there is an urgent need for more effective and safer vaccination strategies. Here, we present a novel mRNA vaccine encoding the CSFV E2 glycoprotein, which provides protective immunity against the CSFV challenge in pigs. Our findings underscore the promising efficacy of this mRNA-based vaccine platform and offer an alternative strategy for CSFV prevention and control.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0097825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959036","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":"Identification of Epstein-Barr virus BORF2 sequences required for APOBEC3B relocalization.","authors":"Farren Clark, Michael A Carpenter, Reuben S Harris, Lori Frappier","doi":"10.1128/jvi.00693-25","DOIUrl":"10.1128/jvi.00693-25","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a common herpesvirus that establishes lifetime infections in most people worldwide. To protect the lytically replicating EBV genomes from mutation, the EBV BORF2 protein relocalizes the APOBEC3B cytosine deaminase out of the nucleus, sequestering it in cytoplasmic bodies. This property is conserved in BORF2 homologs in other herpesviruses, including Kaposi's sarcoma-associated herpesvirus ORF61 and herpes simplex virus 1 UL39. Here, we show that a motif conserved in these three proteins (IPAM) is critical for interactions with and relocalization of APOBEC3B. However, the properties of the cytoplasmic bodies formed by BORF2, ORF61, and UL39 differ in that only BORF2 requires APOBEC3B to form cytoplasmic bodies, and only UL39 bodies have properties of aggresomes. We also found that a SUMO-modified site in BORF2 (K741) plays an important role in the formation of bodies with endogenous APOBEC3B, both when expressed on its own and in the context of EBV infection. Additionally, nuclear BORF2-APOBEC3B bodies that formed in early lytic infection contained SUMO, suggesting the importance of SUMOylation in the sequestration of APOBEC3B. Our study provides insights into the mechanisms herpesviruses use to disable APOBEC3B and protect their replicating DNA genomes from undesired editing.IMPORTANCEHerpesviruses must protect their replicating DNA genomes from mutation by APOBEC3B, which they do by relocalizing APOBEC3B from the nucleus into cytoplasmic bodies. This is mediated by Epstein-Barr virus BORF2 and its homologs in Kaposi's sarcoma-associated herpesvirus (ORF61) and herpes simplex virus 1 (UL39). We have shown that a conserved motif in these proteins is critical for this function, and that a SUMO-modified site in BORF2 also plays an important role. This work provides insight into the mechanisms by which BORF2 and its homologs sequester and relocalize APOBEC3B, which is important for maintaining the integrity and infectivity of the respective herpesviruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0069325"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959095","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":"Permissiveness of different TMEM154 genotype cell lines to different SRLV genotypes/subtypes.","authors":"Barbara Colitti, Daniele Avanzato, Riccardo Moretti, Irati Moncayola, Margherita Profiti, Stefania Chessa, Paola Sacchi, Sergio Rosati, Ramses Reina","doi":"10.1128/jvi.00961-25","DOIUrl":"10.1128/jvi.00961-25","url":null,"abstract":"<p><p>Small ruminant lentiviruses (SRLVs) are a heterogeneous group of viruses that infect goats and sheep worldwide, for which no cures or effective vaccines are available. Control measures have been based on early diagnosis and accurate management with limited success due to re-emergence of seropositivity and disease in controlled flocks. Association between the genetic variation in the ovine transmembrane 154 (<i>TMEM154</i>) gene and susceptibility to certain viral subtypes was previously demonstrated, representing a possible control strategy to reduce infection prevalence in sheep. Thus, the identification of the resistance spectrum of E35K SNP within <i>TMEM154</i> genotypes toward SRLV subtypes becomes crucial. In this study, 10 skin fibroblastic cell lines, from animals encoding three genotypes of the <i>TMEM154</i> (E35K) SNP, were infected with 8 SRLV viral strains and tested for the presence of retrotranscriptase (RT) activity and cytopathic effect. Additionally, SRLV entry into cells was evaluated using viral pseudotypes. Two out of the eight viral strains showed fewer syncytia, reduced cell fusion degree, and lower RT activity in the supernatant of homozygous KK cell lines, suggesting a resistant pattern in these cells. The entry assay revealed a statistically significant difference between the three cell lines in seven of the eight strains, suggesting an entry blockade as the primary restriction factor in KK cells. These findings support the potential use of the <i>TMEM154</i> gene as a marker for the genetic selection of resistant animals to specific SRLV subtypes. Moreover, the <i>ex vivo</i> approach was validated as a valuable tool for studying resistance patterns against different SRLV strains.IMPORTANCESmall ruminant lentiviruses are worldwide spread pathogens that impact animal health and result in severe economic losses. Considering the high genetic and antigenic variability of these viruses and the absence of an effective cure or vaccine, the genetic selection of resistant animals based on the <i>TMEM154</i> gene represents an interesting opportunity to control the infection. Thus, this study aimed to investigate further the host-pathogen interaction considering the association between the animal genotype for the suggested protective mutation and the infecting virus genotype using an <i>in vitro</i> model. The study confirmed <i>TMEM154</i> genetic variation as a helpful predictive factor for SRLV susceptibility by particular SRLV strains including the highly pathogenic B1 subtype, while susceptibility to some A and the B2 subtypes was not affected by the <i>TMEM154</i> gene. Once more, it highlighted the importance of monitoring circulating viral variants for the effective control of SRLV infection through genetic selection programs.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0096125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959210","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":"Baculovirus 25K hijacks host UAP56 to facilitate nuclear export of viral mRNA in insect cells.","authors":"Sixuan Xiao, Huizhen Guo, Jiayi Liu, Lihua Wei, Qingqing Yang, Enyu Xie, Bingbing Wang, Qingyou Xia, Liang Jiang","doi":"10.1128/jvi.01248-25","DOIUrl":"https://doi.org/10.1128/jvi.01248-25","url":null,"abstract":"<p><p><i>Bombyx mori</i> nucleopolyhedrovirus (BmNPV) is a baculovirus that hijacks host genes to cause viral infections. UAP56 is highly conserved in different species. Previous studies have shown that UAP56 is involved in several viral infections. However, its role in insect-baculovirus interactions remains unknown. In this study, we aimed to identify which BmNPV proteins interact with host UAP56 and to characterize the associated mechanism underlying viral infection using a BmNPV-silkworm model. Our data indicated that CCT018159, an inhibitor of UAP56, could suppress the proliferation of BmNPV and that the addition of CCT018159 within 12 h post-infection had a significant protective effect on BmE cells. To identify the interacting viral proteins, recombinant UAP56-GST was constructed through prokaryotic expression for pull-down screening. Further, immunofluorescence, co-immunoprecipitation, and pull-down analyses demonstrated that the late viral protein, 25K, directly binds to UAP56. CCT018159 did not affect the co-localization of 25K and UAP56 but disrupted the interaction between them, resulting in significant upregulation of viral mRNA content in the nucleus and opposite trend in the cytoplasm. Overexpression of 25K and UAP56 caused a significant reduction in viral mRNA content in the nucleus and a significant increase in the cytoplasm. The addition of CCT018159 counteracted this effect. Overall, our data show that the baculovirus 25K protein hijacks host UAP56 to facilitate the nuclear export of viral mRNA to cause infections.IMPORTANCENuclear export of viral mRNA is essential for viral proliferation. UAP56 is highly conserved among species and is involved in multiple viral infections. In this study, we found that the <i>Bombyx mori</i> nucleopolyhedrovirus 25K protein hijacks host UAP56 to facilitate viral mRNA nuclear export, and disruption of their interactions can inhibit viral proliferation. Our results provide novel insights into the mechanism of insect-baculovirus interaction and emphasize the important role that 25K plays in baculovirus infection. This research not only deepens our understanding of the transcription and translation mechanisms of baculoviruses but also provides potential targets for antiviral research.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0124825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}