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Type II grass carp reovirus utilizes autophagosomes for viroplasm formation and subclinical persistent infection.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-04-02 DOI: 10.1128/jvi.00352-25
Qian Wang, Zichao Peng, Pengfei Chu, Bin Gui, Yongming Li, Lanjie Liao, Zuoyan Zhu, Fei Ke, Yaping Wang, Libo He
{"title":"Type II grass carp reovirus utilizes autophagosomes for viroplasm formation and subclinical persistent infection.","authors":"Qian Wang, Zichao Peng, Pengfei Chu, Bin Gui, Yongming Li, Lanjie Liao, Zuoyan Zhu, Fei Ke, Yaping Wang, Libo He","doi":"10.1128/jvi.00352-25","DOIUrl":"https://doi.org/10.1128/jvi.00352-25","url":null,"abstract":"<p><p>Grass carp reovirus (GCRV) is the most virulent pathogen within the genus <i>Aquareovirus</i>, belonging to the family <i>Spinareoviridae</i>. GCRV is categorized into three genotypes, with type II (GCRV-II) being the predominant strain circulating in China. Reoviruses are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, information regarding the formation of GCRV-II viroplasms and their specific roles in virus infection remains largely unknown. In this study, we investigated the formation and characteristics of viroplasms during GCRV-II infection. Immunofluorescence and confocal microscopy indicate that GCRV-II infection induces the formation of viroplasms, with the nonstructural protein NS79 being the key protein responsible for this process. Live-cell imaging and fluorescence recovery after photobleaching assays reveal that GCRV-II viroplasms lack liquid-like properties. Transmission electron microscopy confirms that GCRV-II viroplasms are membranous structures. Notably, we demonstrate that GCRV-II infection induces autophagy and the formation of autophagosomes and that GCRV-II utilizes these autophagosomes for viroplasm formation and virion assembly. Furthermore, we found that GCRV-II uses autophagosomes to evade the host immune system, establishing subclinical persistent infection. GCRV-II also employs autophagosomes for nonlytic release and viral spread. Collectively, these findings highlight distinctive characteristics of GCRV-II viroplasms compared to those of other animal reoviruses, offering valuable insights for the prevention and control of this virus.IMPORTANCEGrass carp reovirus (GCRV) is categorized into three genotypes, with GCRV-II being the most prevalent in China. Despite reoviruses being known for their replication and assembly in viroplasms, the specifics of GCRV-II viroplasm formation and its role in infection were unclear. Our study demonstrates that GCRV-II infection triggers the formation of viroplasms, primarily mediated by the nonstructural protein NS79. GCRV-II viroplasms are membranous structures that lack liquid-like properties, which are significantly different from the viroplasms of other reoviruses. Notably, our research unveils that GCRV-II infection induces autophagy and utilizes autophagosomes for viroplasm formation and virion assembly. Furthermore, we also confirm that GCRV-II utilizes autophagosomes for subclinical persistent infection, nonlytic release, and viral spread. Our results indicate that GCRV-II hijacks autophagosomes to form viroplasms and complete its life cycle. The characteristics of GCRV-II are significantly different from those of other animal reoviruses, providing important information for prevention and control of this virus.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0035225"},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764028","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}
引用次数: 0
Proteogenomic analysis of Cyprinid herpesvirus 2 using high-resolution mass spectrometry.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-04-02 DOI: 10.1128/jvi.01960-24
Chen Xu, Fangxing Yu, Mingyang Xue, Zhenyu Huang, Nan Jiang, Yiqun Li, Yan Meng, Wenzhi Liu, Ya Zheng, Yuding Fan, Yong Zhou
{"title":"Proteogenomic analysis of Cyprinid herpesvirus 2 using high-resolution mass spectrometry.","authors":"Chen Xu, Fangxing Yu, Mingyang Xue, Zhenyu Huang, Nan Jiang, Yiqun Li, Yan Meng, Wenzhi Liu, Ya Zheng, Yuding Fan, Yong Zhou","doi":"10.1128/jvi.01960-24","DOIUrl":"https://doi.org/10.1128/jvi.01960-24","url":null,"abstract":"<p><p>Cyprinid herpesvirus 2 (CyHV-2) is the main pathogen responsible for the development of herpesviral hematopoietic necrosis disease (HVHND) in crucian carp (<i>Carassius auratus</i>). The CyHV-2 genome encodes approximately 150 genes that are expressed in a well-defined manner during productive infection. However, CyHV-2 open reading frames (ORFs) are primarily derived from sequence and homology analyses, and most lack protein-level evidence to support their properties. In this study, we used high-resolution mass spectrometry followed by proteogenomic mapping to achieve genome re-annotation of CyHV-2. Based on our results, a total of 1,683 MS/MS spectra could be mapped to the CyHV-2 genome through six-frame translation, with 1,665 corresponding to 117 currently annotated protein-coding ORFs. Three of the remaining 18 peptides were mapped to the N-terminal extension region of known ORFs. However, 12 novel CyHV-2 ORFs, designated nORF1-12, were identified and characterized for the first time based on the remaining 15 peptides that could be mapped to previously unannotated regions of the viral genome. And the sequence differences of the novel phosphorylated nORF1, also referred to as ORF25E, in different CyHV-2 strains indicated that the nORF1 is a prospective molecular marker that can monitor the evolution from the Japan (J) to the China (C) genotype of CyHV-2. These findings further validate existing annotations, expand the genomic landscape of CyHV-2, and provide a rich resource for aquatic virology research.IMPORTANCECyHV-2 is a viral pathogen that poses a significant threat to crucian carp farming. CyHV-2 has a large genome with complex sequence features and diverse coding mechanisms, which complicates accurate genome annotation in the absence of protein-level evidence. Here, we employed various protein extraction and separation methods to increase viral protein coverage and performed an integrated proteogenomic analysis to refine the CyHV-2 genome annotation. A total of 129 viral genes were confidently identified, including 117 currently annotated genes and 12 novel genes. For the first time, we present large-scale evidence of peptide presence and levels in the genome of aquatic viruses and confirm the majority of the predicted proteins in CyHV-2. Our findings enhance the understanding of the CyHV-2 genome structure and provide valuable insights for future studies on CyHV-2 biology.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0196024"},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763847","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}
引用次数: 0
A plant virus attenuates the Toll immune pathway by degradation of Pellino to facilitate viral infection in insect vectors.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.00021-25
Yu-Xiao Du, Yu-Hua Qi, Yan-Hua Lu, Bo-Xue Li, Yu-Juan He, Yan Zhang, Lin Lin, Chuan-Xi Zhang, Xiao-Wei Wang, Jian-Ping Chen, Gang Lu, Jun-Min Li
{"title":"A plant virus attenuates the Toll immune pathway by degradation of Pellino to facilitate viral infection in insect vectors.","authors":"Yu-Xiao Du, Yu-Hua Qi, Yan-Hua Lu, Bo-Xue Li, Yu-Juan He, Yan Zhang, Lin Lin, Chuan-Xi Zhang, Xiao-Wei Wang, Jian-Ping Chen, Gang Lu, Jun-Min Li","doi":"10.1128/jvi.00021-25","DOIUrl":"https://doi.org/10.1128/jvi.00021-25","url":null,"abstract":"<p><p>Many plant viruses are persistently transmitted by insect vectors. The viral antagonism of insect innate immune responses is a critical step in ensuring persistent viral infection. Recent studies have shown that the Toll immune pathway mediates the persistent and propagative transmission of rice stripe virus (RSV) in its insect vector (<i>Laodelphax striatellus</i>). However, whether other host factors are involved in the Toll pathway and how RSV counteracts the Toll immune response in <i>L. striatellus</i> remain unclear. Here, we reported that LsPellino also inhibited RSV infection in <i>L. striatellus</i> by interacting with LsTube and participating in the Toll immune pathway. In contrast, the viral nonstructural protein NS3 hijacked the suppressor of cytokine signaling 5 (LsSOCS5) to promote the degradation of LsPellino via the 26S proteasome pathway, thereby suppressing the Toll immune response. In summary, these findings demonstrate that RSV attenuates the Toll immune pathway by degradation of LsPellino to facilitate viral infection in insect vectors. Our research provides new insights into controlling the transmission of vector-borne viruses.</p><p><strong>Importance: </strong>Plant virus diseases pose a serious threat to global crop production. Nearly half of the known plant viruses are persistently transmitted by insect vectors, and these plant viruses must counteract various innate immune responses to maintain persistent infection. Here, we uncover a novel counter-defense mechanism against Toll antiviral defense. Our research showed that LsPellino exerts antiviral function by interacting with LsTube and participating in the Toll immune pathway. To counteract this immunity, a plant virus, rice stripe virus, attenuates the Toll immune pathway and promotes viral infection by using viral nonstructural protein NS3 to mediate the degradation of LsPellino in its insect vector, <i>Laodelphax striatellus</i>. This study not only contributes to a better understanding of the arms race between viruses and insect vectors but also provides a new perspective for controlling the transmission of plant viruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0002125"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753486","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}
引用次数: 0
Early spatiotemporal evolution of the immune response elicited by adenovirus serotype 26 vector vaccination in mice. 小鼠接种腺病毒血清 26 型载体疫苗引起的免疫反应的早期时空演变。
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.00247-25
Eryn Blass, Alessandro Colarusso, Malika Aid, Rafael A Larocca, R Keith Reeves, Dan H Barouch
{"title":"Early spatiotemporal evolution of the immune response elicited by adenovirus serotype 26 vector vaccination in mice.","authors":"Eryn Blass, Alessandro Colarusso, Malika Aid, Rafael A Larocca, R Keith Reeves, Dan H Barouch","doi":"10.1128/jvi.00247-25","DOIUrl":"https://doi.org/10.1128/jvi.00247-25","url":null,"abstract":"<p><p>As the first responder to immunological challenges, the innate immune system shapes and regulates the ensuing adaptive immune response. Many clinical studies evaluating the role of innate immunity in initiating vaccine-elicited adaptive immune responses have largely been confined to blood due to the inherent difficulty in acquiring tissue samples. However, the absence of vaccine-site and draining lymph node information limits the understanding of early events induced by vaccination that could potentially shape vaccine-elicited immunity. We, therefore, utilized a mouse model to investigate the spatiotemporal evolution of the immune response within the first 24 hours following intramuscular adenovirus serotype 26 (Ad26) vector vaccination in tissues. We show that the Ad26 vaccine-elicited innate immune response commences by 1 hour and rapidly evolves in tissues and blood within the first 24 hours, as reflected by the detection of cytokines, chemokines, cellular responses, and transcriptomic pathways. Furthermore, serum levels of IL-6, MIG, MIP-1α, MIP-1β, and TNF-α at 6 hours post-vaccination correlated with the frequency of vaccine-elicited memory CD8<sup>+</sup> T cell responses evaluated at 60 days post-vaccination in blood and tissues. Taken together, our data suggest that the immune response to Ad26 vector vaccination commences quickly in tissues by 1 hour and that events by as early as 6 hours post-vaccination can shape vaccine-elicited CD8<sup>+</sup> T cell responses at later memory time points.IMPORTANCEPrior studies have largely concentrated on innate immune activation in peripheral blood following vaccination. In this study, we report the detailed spatial and temporal innate immune activation in tissues following Ad26 vaccination in mice. We observed rapid innate activation not only in peripheral blood but also in draining lymph nodes and at the site of inoculation. Our findings provide a more detailed picture of the host response to vaccination than previously reported.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0024725"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753491","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}
引用次数: 0
Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.01668-24
Roshan Ghimire, Rakshya Shrestha, Radhika Amaradhi, Lin Liu, Sunil More, Thota Ganesh, Alexandra K Ford, Rudragouda Channappanavar
{"title":"Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.","authors":"Roshan Ghimire, Rakshya Shrestha, Radhika Amaradhi, Lin Liu, Sunil More, Thota Ganesh, Alexandra K Ford, Rudragouda Channappanavar","doi":"10.1128/jvi.01668-24","DOIUrl":"https://doi.org/10.1128/jvi.01668-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced impaired antiviral immunity and excessive inflammatory responses cause lethal pneumonia. However, the &lt;i&gt;in vivo&lt;/i&gt; roles of key pattern recognition receptors that elicit protective antiviral and fatal inflammatory responses, specifically in the lungs, are not well described. Coronaviruses possess single-stranded RNA genome that activates TLR7/8 to induce an antiviral interferon (IFN) and robust inflammatory cytokine response. Here, using wild-type and TLR7-deficient (TLR7&lt;sup&gt;-/-&lt;/sup&gt;) mice infected with mouse-adapted SARS-CoV-2 (MA-CoV-2), we examined the role of TLR7 in the lung antiviral and inflammatory response and severe pneumonia. We showed that TLR7 deficiency significantly increased lung virus loads and morbidity/mortality, which correlated with reduced levels of type I IFNs (&lt;i&gt;Ifna/b&lt;/i&gt;), type III IFNs (&lt;i&gt;Ifnl&lt;/i&gt;), and IFN-stimulated genes (ISGs) in the lungs. A detailed evaluation of MA-CoV-2-infected lungs revealed increased neutrophil accumulation and lung pathology in TLR7&lt;sup&gt;-/-&lt;/sup&gt; mice. We further showed that blocking type I IFN receptor (IFNAR) signaling enhanced SARS-CoV-2 replication in the lungs and caused severe lung pathology, leading to 100% mortality compared to infected control mice. Moreover, immunohistochemical assessment of the lungs revealed increased numbers of SARS-CoV-2 antigen-positive macrophages, pneumocytes, and bronchial epithelial cells in TLR7&lt;sup&gt;-/-&lt;/sup&gt; and IFNAR-deficient mice compared to control mice. In summary, we conclusively demonstrated that despite TLR7-induced robust lung inflammation, TLR7-induced IFN/ISG responses suppress lung virus replication and pathology and provide protection against SARS-CoV-2-induced fatal pneumonia. Additionally, given the similar disease outcomes in control, TLR7&lt;sup&gt;-/-&lt;/sup&gt;, and IFNAR-deficient MA-CoV-2-infected mice and coronavirus disease 2019 (COVID-19) patients, we propose that MA-CoV-2-infected mice constitute an excellent model for studying COVID-19.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is caused by a delicate balance between a strong antiviral and an exuberant inflammatory response. A robust antiviral immunity and regulated inflammation are protective, while a weak antiviral response and excessive inflammation are detrimental. However, the key host immune sensors that elicit protective antiviral and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge are poorly defined. Here, we examined the role of viral RNA-mediated TLR7 activation in the lung antiviral and inflammatory responses in SARS-CoV-2-infected mice. We demonstrate that TLR7 deficiency led to a high rate of morbidity and mortality, which correlated with an impaired antiviral interferon (IFN)-I/III response, enhanced lung virus replication, and severe lung pathology. Furthermore, we show that blocking IFN-I signaling using anti-IFN receptor antibody promo","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0166824"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753538","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}
引用次数: 0
Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy. 热休克蛋白A1通过伴侣介导的自噬作用降解病毒RNA聚合酶3D,从而抑制口蹄疫病毒的复制。
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.00168-25
Mei Ren, Haiqian Zhou, Jin-En Wu, Jia-Ning Wang, Xuefei Wang, Sahibzada Waheed Abdullah, Huichen Guo, Shiqi Sun
{"title":"Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.","authors":"Mei Ren, Haiqian Zhou, Jin-En Wu, Jia-Ning Wang, Xuefei Wang, Sahibzada Waheed Abdullah, Huichen Guo, Shiqi Sun","doi":"10.1128/jvi.00168-25","DOIUrl":"https://doi.org/10.1128/jvi.00168-25","url":null,"abstract":"<p><p>Foot-and-mouth disease virus (FMDV), a member of the <i>Picornaviridae</i> family, is a single-stranded, positive-sense RNA virus. Heat shock protein A1 (HSPA1) has been shown to influence the entry, translation, assembly, and release of enterovirus A71 (EV-A71), another <i>Picornaviridae</i> family member. In this study, we demonstrate that HSPA1 plays a different role in the replication of FMDV. By investigating various stages of virus replication, we found that HSPA1 specifically inhibits the RNA replication stage in which HSPA1 inhibits viral RNA replication by degrading the viral RNA-dependent RNA polymerase (RdRp), 3D protein. In the presence of specific inhibitors, we find out that this degradation occurs through the autophagy pathway. Activation and blockage of chaperone-mediated autophagy (CMA) demonstrate that HSPA1 degrades 3D through the CMA pathway. Mutation analysis reveals that <sub>421</sub>QEKLI<sub>425</sub> is the key motif in 3D responsible for HSPA1-mediated CMA degradation. In summary, this study shows that HSPA1 can degrade the viral 3D protein through the CMA pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp, revealing the crucial role of HSPA1 in the FMDV infection process and suggesting that HSPA1 could be a potential target for the prevention and treatment of FMDV infection.</p><p><strong>Importance: </strong>Viral RNA replication is the key stage in understanding the pathogenic mechanisms of foot-and-mouth disease virus (FMDV). During this process, the viral non-structural protein 3D serves as an RNA-dependent RNA polymerase (RdRp) to synthesize progeny RNA using the viral genomic RNA as a template. However, the regulatory effect of host cells on FMDV 3D proteins has not yet been studied. In this study, we find that heat shock protein A1 (HSPA1) degrades the viral 3D protein through the chaperone-mediated autophagy (CMA) pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0016825"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753441","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}
引用次数: 0
The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.00004-25
Qiaozhi Zhao, Pan Pan, Lirong Mo, Jiangtao Wu, Shengjie Liao, Hua Lu, Qiwei Zhang, Xiaoshen Zhang
{"title":"The ELF3-TRIM22-MAVS signaling axis regulates type I interferon and antiviral responses.","authors":"Qiaozhi Zhao, Pan Pan, Lirong Mo, Jiangtao Wu, Shengjie Liao, Hua Lu, Qiwei Zhang, Xiaoshen Zhang","doi":"10.1128/jvi.00004-25","DOIUrl":"https://doi.org/10.1128/jvi.00004-25","url":null,"abstract":"<p><p>Activation of the innate immune response is essential for host cells to restrict the dissemination of invading viruses and other pathogens. Proteins belonging to the tripartite motif (TRIM) family are key effectors in antiviral innate immunity. Among these, TRIM22, a RING-type E3 ubiquitin ligase, has been recognized as a significant regulator in the pathogenesis of various diseases. In the present study, we identified TRIM22 as a critical modulator of mitochondrial antiviral signaling protein (MAVS) activation. Loss of TRIM22 function led to reduced production of type I interferons (IFNs) in response to viral infection such as influenza A virus (IAV) or vesicular stomatitis virus (VSV), thereby facilitating viral replication. Mechanistically, TRIM22 was found to enhance retinoic acid-inducible gene I (RIG-I)-mediated signaling through the catalysis of Lys63-linked polyubiquitination of MAVS, which, in turn, activated the TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) pathway, driving IFN-β production. Additionally, TRIM22 was shown to inhibit the assembly of the MAVS-NLRX1 inhibitory complex, further amplifying innate immune responses. Our findings also demonstrated that RNA virus infection upregulated TRIM22 expression via the nuclear translocation of ELF3, a transcription factor that activates TRIM22 gene expression. This regulatory loop underscores the role of TRIM22 in modulating the type I IFN pathway, providing critical insights into the host's antiviral defense mechanisms. Our research highlights the potential of targeting the ELF3-TRIM22-MAVS axis as a therapeutic strategy for enhancing antiviral immunity and preventing RNA virus infections.IMPORTANCEInterferon (IFN)-mediated antiviral responses are crucial for the host's defense against foreign pathogens and are regulated by various signaling pathways. The tripartite motif (TRIM) family, recognized for its multifaceted roles in immune regulation and antiviral defense, plays a significant part in this process. In our study, we explored the important role of TRIM22, a protein that helped regulate the host's immune response to viral infections. We found that TRIM22 enhances the Lys63-linked polyubiquitination of mitochondrial antiviral signaling protein (MAVS), which was essential for producing type I interferons. Interestingly, we discovered that the expression of TRIM22 increases after an RNA virus infection, due to a transcription factor ELF3, which moved into the nucleus of cells to activate TRIM22 transcription. This created a feedback loop that strengthens the role of TRIM22 in modulating the type I IFN pathway. By uncovering these mechanisms, we aimed to enhance our understanding of how the immune system works and provide insights that could lead to innovative antiviral therapies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0000425"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753581","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}
引用次数: 0
The S273R protein of African swine fever virus antagonizes the canonical NF-κB signaling pathway by IκBα.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.02225-24
Haojie Ren, Lan-Fang Shi, Yanjin Wang, Xiao-Ya Pan, Su Li, Yu-He Ma, Jun-Hao Fan, Xing Chen, Zhong-Yuan Yang, Shuai Fan, Yuhang Zhang, Shichong Han, Wen-Rui He, Bo Wan, Hua-Ji Qiu, Gai-Ping Zhang
{"title":"The S273R protein of African swine fever virus antagonizes the canonical NF-<i>κ</i>B signaling pathway by I<i>κ</i>B<i>α</i>.","authors":"Haojie Ren, Lan-Fang Shi, Yanjin Wang, Xiao-Ya Pan, Su Li, Yu-He Ma, Jun-Hao Fan, Xing Chen, Zhong-Yuan Yang, Shuai Fan, Yuhang Zhang, Shichong Han, Wen-Rui He, Bo Wan, Hua-Ji Qiu, Gai-Ping Zhang","doi":"10.1128/jvi.02225-24","DOIUrl":"https://doi.org/10.1128/jvi.02225-24","url":null,"abstract":"<p><p>African swine fever virus (ASFV) is a large double-stranded DNA virus, which is the causative agent of African swine fever (ASF), a devastating disease of suids epidemic in many countries. The virus has developed multiple strategies to evade surveillance from the host immune system. Inflammatory responses, especially the NF-<i>κ</i>B signaling pathway, play central roles in ASFV pathogenesis and immunoevasion. In this study, we identified the ASFV S273R protein (pS273R) as an antagonist of the canonical NF-<i>κ</i>B signaling pathway independently of its protease activity. The ectopically expressed pS273R markedly inhibited the tumor necrosis factor-alpha or interleukin-1 beta-triggered NF-<i>κ</i>B signaling pathway in HEK293T and PK-15 cells. Silencing pS273R by RNA interference led to elevated expression levels of proinflammatory cytokines in the ASFV-infected primary porcine alveolar macrophages. Mechanistically, pS273R functioned independently of its protease activity. pS273R was associated with the NF-<i>κ</i>B complex and interrupted the translocation of I<i>κ</i>B<i>α</i> into the proteasome, resulting in the increased stability of I<i>κ</i>B<i>α</i> and subsequently impaired nuclear translocation of p65. Furthermore, the core domain (amino acids 83-273) of pS273R was essential for the pS273R-mediated inhibition of the NF-<i>κ</i>B signaling pathway. These findings demonstrate the immunosuppressive role of pS273R and provide novel insights into ASFV biological characteristics.IMPORTANCEAfrican swine fever (ASF) is a hemorrhagic disease of suids caused by African swine fever virus (ASFV), with morbidity and mortality rates of up to 100%. The disease has led to significant economic losses to the global swine industry. In this study, we identify the ASFV S273R protein (pS273R) as an antagonist of the canonical NF-<i>κ</i>B signaling pathway. Our findings demonstrate the immunosuppressive role of pS273R, which will contribute to a better understanding of the pathogenesis of ASFV and may contribute to the development of antiviral therapies against ASF.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0222524"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753596","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}
引用次数: 0
The two-dose MVA-BN mpox vaccine induces a nondurable and low avidity MPXV-specific antibody response.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.00253-25
Aaron L Oom, Kesi K Wilson, Miilani Yonatan, Stephanie Rettig, Heekoung Allison Youn, Michael Tuen, Yusra Shah, Ashley L DuMont, Hayley M Belli, Jane R Zucker, Jennifer B Rosen, Ramin Sedaghat Herati, Marie I Samanovic, Ralf Duerr, Angelica C Kottkamp, Mark J Mulligan
{"title":"The two-dose MVA-BN mpox vaccine induces a nondurable and low avidity MPXV-specific antibody response.","authors":"Aaron L Oom, Kesi K Wilson, Miilani Yonatan, Stephanie Rettig, Heekoung Allison Youn, Michael Tuen, Yusra Shah, Ashley L DuMont, Hayley M Belli, Jane R Zucker, Jennifer B Rosen, Ramin Sedaghat Herati, Marie I Samanovic, Ralf Duerr, Angelica C Kottkamp, Mark J Mulligan","doi":"10.1128/jvi.00253-25","DOIUrl":"https://doi.org/10.1128/jvi.00253-25","url":null,"abstract":"<p><p>The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, public health officials began vaccination campaigns using the third-generation orthopoxvirus vaccine modified vaccinia Ankara from Bavarian Nordic (MVA-BN). Prior to this outbreak, the durability of monkeypox virus (MPXV)-specific immunity induced by MVA-BN was poorly understood. In 2022, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI, NCT05654883), a longitudinal study of 171 participants comprising MVA-BN vaccines and mpox convalescent individuals. Peripheral blood sampling was performed at intervals including prior to vaccination, after one dose, and after the second dose. MVA-BN vaccinees with and without a history of smallpox vaccination demonstrated detectable MPXV-specific memory B cells at 1-year post-vaccination. Additionally, MVA-BN increased MPXV neutralizing titers in smallpox vaccine-naïve vaccinees, with a comparable maximum titer reached in naïve and smallpox vaccine-experienced vaccinees. However, neutralizing titers returned to baseline within 5-7 months for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generated robust IgG responses against MPXV H3 and A35, but naïve vaccinees' IgG responses showed lower avidity than experienced vaccinees. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This work supports the need for long-term studies on protection induced by MVA-BN, including the potential need for booster doses as well as the development of next-generation orthopoxvirus vaccines.</p><p><strong>Importance: </strong>The ongoing outbreaks of mpox demonstrate the continuing threat of orthopoxviruses to global health. While previous orthopoxvirus vaccines generated lifelong antibody and cellular immunity, we show here that the current mpox vaccine, MVA-BN or JYNNEOS, fails to induce durable antibody immunity in individuals with no prior smallpox vaccination. This raises the important question of whether MVA-BN vaccinees have long-term protection from mpox. Our work highlights the need for further studies into the durability of protection generated by MVA-BN as well as whether subsequent booster doses are necessary to maintain protection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0025325"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753600","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}
引用次数: 0
A novel tobamo-like mycovirus with filamentous particles replicates in plant cells.
IF 4 2区 医学
Journal of Virology Pub Date : 2025-03-31 DOI: 10.1128/jvi.02102-24
Meilian Hong, Fengjuan Tian, Zhenmei Song, Hongmei Liu, Yigang Tong, Tingting Zhang
{"title":"A novel tobamo-like mycovirus with filamentous particles replicates in plant cells.","authors":"Meilian Hong, Fengjuan Tian, Zhenmei Song, Hongmei Liu, Yigang Tong, Tingting Zhang","doi":"10.1128/jvi.02102-24","DOIUrl":"https://doi.org/10.1128/jvi.02102-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Parasitic and symbiotic plant-fungus relationships have existed for millions of years, and phylogenetic analyses of certain virus families indicate transmission between plants and fungi. A group of tobamo-like viruses from various fungi has recently been identified. Tobamo-like viruses are homologous to plant viruses of the &lt;i&gt;Tobamovirus&lt;/i&gt; genus in the &lt;i&gt;Virgaviridae&lt;/i&gt; family, but it was unknown whether they form typical virus particles and can replicate and exhibit cell-to-cell movement in plants. Here, a novel tobamo-like virus, Nigrospora aurantiaca tobamo-like virus 1 (NaTLV1), obtained from the phytopathogenic fungus &lt;i&gt;Nigrospora aurantiaca&lt;/i&gt;, was characterized. Its genome (10,301 nucleotides) comprises four open reading frames (ORFs) and a poly(A) tail. ORF1 encodes a methyltransferase and helicase, and ORF2 encodes RNA-dependent RNA polymerase, which are closely related to proteins of &lt;i&gt;Virgaviridae&lt;/i&gt; viruses. ORF3 encodes a putative movement protein, and ORF4 encodes a putative coat protein, which are closely related to proteins of &lt;i&gt;Gammaflexiviridae&lt;/i&gt; and &lt;i&gt;Betaflexiviridae&lt;/i&gt; viruses. NaTLV1 formed filamentous virus particles and could replicate in &lt;i&gt;Nicotiana benthamiana&lt;/i&gt;. However, the cell-to-cell movement of NaTLV1 was not observed in &lt;i&gt;N. benthamiana&lt;/i&gt; but could not be ruled out. NaTLV1 underwent horizontal and vertical transmissions via hyphal anastomosis and conidia, respectively. There were no significant differences in phenotype or virulence between NaTLV1-infected (A4) and NaTLV1-free (V1) &lt;i&gt;N. aurantiaca&lt;/i&gt; strains. In general, our findings may be useful in elucidating the origination and evolution of tobamo-like viruses, plant virus families (&lt;i&gt;Virgaviridae&lt;/i&gt; and &lt;i&gt;Betaflexiviridae&lt;/i&gt;), and a fungal virus family (&lt;i&gt;Gammaflexiviridae&lt;/i&gt;).IMPORTANCECross-kingdom infections involving plant- and fungal-associated viruses have been directly observed in nature, and some of these viruses share a high degree of genetic similarity. A group of novel tobamo-like viruses with nonsegmented single-stranded RNA genomes was recently isolated from diverse fungal groups. Here, we identified a novel virus, Nigrospora aurantiaca tobamo-like virus 1 (NaTLV1), in the phytopathogenic fungus &lt;i&gt;Nigrospora aurantiaca&lt;/i&gt;. NaTLV1 was phylogenetically related to other tobamo-like viruses, plant-associated viruses in the &lt;i&gt;Virgaviridae&lt;/i&gt; and &lt;i&gt;Betaflexiviridae&lt;/i&gt; families, and fungus-associated viruses in the &lt;i&gt;Gammaflexiviridae&lt;/i&gt; family. NaTLV1 formed filamentous virus particles and could replicate in &lt;i&gt;Nicotiana benthamiana,&lt;/i&gt; but the cell-to-cell movement of NaTLV1 was not observed. This study provides potential insights into the origins and evolution of mycoviruses originating from plant viruses and indicates that tobamo-like viruses may have adapted to an intracellular lifestyle during evolution. The identification of novel tobamo-like viruses is crucial for understanding fungal and plant virus evo","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0210224"},"PeriodicalIF":4.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753481","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}
引用次数: 0
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