Journal of General Virology最新文献

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Tissue distribution and transmission of Rift Valley fever phlebovirus in European Culex pipiens and Aedes albopictus mosquitoes following intrathoracic inoculation. 欧洲库蚊和白纹伊蚊胸腔内接种后裂谷热细小病毒的组织分布和传播。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-09-01 DOI: 10.1099/jgv.0.002025
Jaume Gardela, Karen Yautibug, Sandra Talavera, Enric Vidal, Catherine Cêtre Sossah, Nonito Pagès, Núria Busquets
{"title":"Tissue distribution and transmission of Rift Valley fever phlebovirus in European <i>Culex pipiens</i> and <i>Aedes albopictus</i> mosquitoes following intrathoracic inoculation.","authors":"Jaume Gardela, Karen Yautibug, Sandra Talavera, Enric Vidal, Catherine Cêtre Sossah, Nonito Pagès, Núria Busquets","doi":"10.1099/jgv.0.002025","DOIUrl":"10.1099/jgv.0.002025","url":null,"abstract":"<p><p>Rift Valley fever virus (<i>Phlebovirus riftense</i>, RVFV) poses significant economic challenges, particularly in African nations, causing substantial livestock losses and severe haemorrhagic disease in humans. In Europe, the risk of RVFV transmission is deemed moderate due to the presence of competent vectors like <i>Culex pipiens</i> and <i>Aedes albopictus</i>, along with susceptible animal vertebrate hosts across member states. This study investigates RVFV infection dynamics in European mosquito populations, aiming to enhance our understanding of their vectorial capacity and virus transmission, which can be useful for future investigations to improve RVFV surveillance, control programmes, and preventive treatments. Intrathoracic inoculation of European <i>Cx. pipiens</i> and <i>Ae. albopictus</i> with an RVFV virulent strain (RVF 56/74) enabled the assessment of virus tissue distribution and transmission. Immunohistochemistry analyses revealed widespread RVFV infection in all analysable anatomical structures at 5 and 14 days post-inoculation. Notably, the ganglionic nervous system exhibited the highest detection of RVFV in both species. <i>Cx. pipiens</i> showed more frequently infected structures than <i>Ae. albopictus</i>, particularly in reproductive structures. The identification of an RVFV-positive egg follicle in <i>Cx. pipiens</i> hints at potential vertical transmission. Saliva analysis indicated a higher transmission potential in <i>Cx. pipiens</i> (71.4%) compared to <i>Ae. albopictus</i> (4.3%) at the early time point. This study offers the first description and comparison of RVFV tissue distribution in <i>Ae. albopictus</i> and <i>Cx. pipiens</i>, shedding light on the susceptibility of their nervous systems, which may alter mosquito behaviour, which is critical for virus transmission. Overall, enhancing our knowledge of viral infection within mosquitoes holds promise for future vector biology research and innovative approaches to mitigate RVFV transmission.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation. 软疣病毒蛋白 MC089 可抑制干扰素调节因子 3 的激活。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002015
Mariya Al Hamrashdi, Carla Sanchez Perez, Darya A Haas, Jyoti Vishwakarma, Andreas Pichlmair, Andrew G Bowie, Gareth Brady
{"title":"Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation.","authors":"Mariya Al Hamrashdi, Carla Sanchez Perez, Darya A Haas, Jyoti Vishwakarma, Andreas Pichlmair, Andrew G Bowie, Gareth Brady","doi":"10.1099/jgv.0.002015","DOIUrl":"10.1099/jgv.0.002015","url":null,"abstract":"<p><p>Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes a highly common but mild infection characterized by distinctive and persistent papular skin lesions. These lesions can persist for long periods without an effective clearance response from the host. MCV, like all poxviruses, encodes multiple known immunosuppressive proteins which target innate immune signalling pathways involved in viral nucleic acid sensing, interferon production and inflammation which should trigger antiviral immunity leading to clearance. Two major families of transcription factors responsible for driving the immune response to viruses are the NF-κB and the interferon regulatory factor (IRF) families. While NF-κB broadly drives pro-inflammatory gene expression and IRFs chiefly drive interferon induction, both collaborate in transactivating many of the same genes in a concerted immune response to viral infection. Here, we report that the MCV protein MC089 specifically inhibits IRF activation from both DNA- and RNA-sensing pathways, making it the first characterized MCV inhibitor to selectively target IRF activation to date. MC089 interacts with proteins required for IRF activation, namely IKKε, TBKBP1 and NAP1. Additionally, MC089 targets RNA sensing by associating with the RNA-sensing adaptor protein mitochondrial antiviral-signalling protein on mitochondria. MC089 displays specificity in its inhibition of IRF3 activation by suppressing immunostimulatory nucleic acid-induced serine 396 phosphorylation without affecting the phosphorylation of serine 386. The selective interaction of MC089 with IRF-regulatory proteins and site-specific inhibition of IRF3 phosphorylation may offer a tool to provide novel insights into the biology of IRF3 regulation.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mouse cytomegalovirus lacking sgg1 shows reduced import into the salivary glands. 缺乏 sgg1 的小鼠巨细胞病毒对唾液腺的输入减少。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002013
Jiawei Ma, Kimberley Bruce, Philip G Stevenson, Helen E Farrell
{"title":"Mouse cytomegalovirus lacking sgg1 shows reduced import into the salivary glands.","authors":"Jiawei Ma, Kimberley Bruce, Philip G Stevenson, Helen E Farrell","doi":"10.1099/jgv.0.002013","DOIUrl":"10.1099/jgv.0.002013","url":null,"abstract":"<p><p>Cytomegaloviruses (CMVs) transmit via chronic shedding from the salivary glands. How this relates to the broad cell tropism they exhibit <i>in vitro</i> is unclear. Human CMV (HCMV) infection presents only after salivary gland infection is established. Murine CMV (MCMV) is therefore useful to analyse early infection events. It reaches the salivary glands via infected myeloid cells. Three adjacent spliced genes designated as m131/129 (MCK-2), sgg1 and sgg1.1, positional homologues of the HCMV UL128/130/131 tropism determinants, are implicated. We show that a sgg1 null mutant is defective in infected myeloid cell entry into the salivary glands, a phenotype distinct from MCMV lacking MCK-2. These data point to a complex, multi-step process of salivary gland colonization.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eilat virus (EILV) causes superinfection exclusion against West Nile virus (WNV) in a strain-specific manner in Culex tarsalis mosquitoes. 埃拉特病毒(EILV)在跗线库蚊中以特异性毒株的方式对西尼罗河病毒(WNV)造成超感染排斥。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002017
Renuka E Joseph, Jovana Bozic, Kristine L Werling, Rachel S Krizek, Nadya Urakova, Jason L Rasgon
{"title":"Eilat virus (EILV) causes superinfection exclusion against West Nile virus (WNV) in a strain-specific manner in <i>Culex tarsalis</i> mosquitoes.","authors":"Renuka E Joseph, Jovana Bozic, Kristine L Werling, Rachel S Krizek, Nadya Urakova, Jason L Rasgon","doi":"10.1099/jgv.0.002017","DOIUrl":"10.1099/jgv.0.002017","url":null,"abstract":"<p><p>West Nile virus (WNV) is the leading cause of mosquito-borne illness in the USA. There are currently no human vaccines or therapies available for WNV, and vector control is the primary strategy used to control WNV transmission. The WNV vector <i>Culex tarsalis</i> is also a competent host for the insect-specific virus (ISV) Eilat virus (EILV). ISVs such as EILV can interact with and cause superinfection exclusion (SIE) against human pathogenic viruses in their shared mosquito host, altering vector competence for these pathogenic viruses. The ability to cause SIE and their host restriction make ISVs a potentially safe tool to target mosquito-borne pathogenic viruses. In the present study, we tested whether EILV causes SIE against WNV in mosquito C6/36 cells and <i>C. tarsalis</i> mosquitoes. The titres of both WNV strains - WN02-1956 and NY99 - were suppressed by EILV in C6/36 cells as early as 48-72 h post-superinfection at both m.o.i. values tested in our study. The titres of WN02-1956 at both m.o.i. values remained suppressed in C6/36 cells, whereas those of NY99 showed some recovery towards the final timepoint. The mechanism of SIE remains unknown, but EILV was found to interfere with NY99 attachment in C6/36 cells, potentially contributing to the suppression of NY99 titres. However, EILV had no effect on the attachment of WN02-1956 or internalization of either WNV strain under superinfection conditions. In <i>C. tarsalis</i>, EILV did not affect the infection rate of either WNV strain at either timepoint. However, in mosquitoes<i>,</i> EILV enhanced NY99 infection titres at 3 days post-superinfection, but this effect disappeared at 7 days post-superinfection. In contrast, WN02-1956 infection titres were suppressed by EILV at 7 days post-superinfection. The dissemination and transmission of both WNV strains were not affected by superinfection with EILV at either timepoint. Overall, EILV caused SIE against both WNV strains in C6/36 cells; however, in <i>C. tarsalis</i>, SIE caused by EILV was strain specific potentially owing to differences in the rate of depletion of shared resources by the individual WNV strains.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating the effect of reduced temperatures on the efficacy of rhabdovirus-based viral vector platforms. 研究降低温度对基于横纹肌病毒的病毒载体平台功效的影响。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002010
Julia E Kakish, Yeganeh Mehrani, Arthane Kodeeswaran, Katrina Geronimo, Mary Ellen Clark, Jacob P van Vloten, Khalil Karimi, Bonnie A Mallard, Baozhong Meng, Byram W Bridle, Jason P Knapp
{"title":"Investigating the effect of reduced temperatures on the efficacy of rhabdovirus-based viral vector platforms.","authors":"Julia E Kakish, Yeganeh Mehrani, Arthane Kodeeswaran, Katrina Geronimo, Mary Ellen Clark, Jacob P van Vloten, Khalil Karimi, Bonnie A Mallard, Baozhong Meng, Byram W Bridle, Jason P Knapp","doi":"10.1099/jgv.0.002010","DOIUrl":"10.1099/jgv.0.002010","url":null,"abstract":"<p><p>Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures <i>in vivo</i>, including temperatures ≤31 °C. Despite potential implications, the effect of temperatures <37 °C on the performance of rhabdoviral vectors is unknown. We investigated the effect of low anatomical temperatures on two rhabdoviruses, vesicular stomatitis virus (VSV) and Maraba virus (MG1). Using a metabolic resazurin assay, VSV- and MG1-mediated oncolysis was characterized in a panel of cell lines at 28, 31, 34 and 37 °C. The oncolytic ability of both viruses was hindered at 31 and 28 °C. Cold adaptation of both viruses was attempted as a mitigation strategy. Viruses were serially passaged at decreasing temperatures in an attempt to induce mutations. Unfortunately, the cold-adaptation strategies failed to potentiate the oncolytic activity of the viruses at temperatures <37 °C. Interestingly, we discovered that viral replication was unaffected at low temperatures despite the abrogation of oncolytic activity. In contrast, the proliferation of cancer cells was reduced at low temperatures. Equivalent oncolytic effects could be achieved if cells at low temperatures were treated with viruses for longer times. This suggests that rhabdovirus-mediated oncolysis could be compromised at low temperatures <i>in vivo</i> where therapeutic windows are limited.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic and antigenic characterization of two diarrhoeicdominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population. 全球马群中流行的两种腹泻型轮状病毒 A 基因型 G3P[12] 和 G14P[12] 的遗传和抗原特征。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002016
Tirth Uprety, Shalini Soni, Chithra Sreenivasan, Ben M Hause, Ahsan Naveed, Shuisong Ni, Amy J Graves, Jennifer K Morrow, Nathan Meade, Kenneth H Mellits, Emma Adam, Michael A Kennedy, Dan Wang, Feng Li
{"title":"Genetic and antigenic characterization of two diarrhoeicdominant rotavirus A genotypes G3P[12] and G14P[12] circulating in the global equine population.","authors":"Tirth Uprety, Shalini Soni, Chithra Sreenivasan, Ben M Hause, Ahsan Naveed, Shuisong Ni, Amy J Graves, Jennifer K Morrow, Nathan Meade, Kenneth H Mellits, Emma Adam, Michael A Kennedy, Dan Wang, Feng Li","doi":"10.1099/jgv.0.002016","DOIUrl":"10.1099/jgv.0.002016","url":null,"abstract":"<p><p>Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013-2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an <i>in vitro</i> broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of pH on the structure of Bluetongue virus VP5. pH 值对蓝舌病病毒 VP5 结构的影响。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002018
Hanwen Zhang, Kamel El Omari, Geoff Sutton, David I Stuart
{"title":"The effect of pH on the structure of Bluetongue virus VP5.","authors":"Hanwen Zhang, Kamel El Omari, Geoff Sutton, David I Stuart","doi":"10.1099/jgv.0.002018","DOIUrl":"10.1099/jgv.0.002018","url":null,"abstract":"<p><p>The unenveloped Bluetongue virus capsid comprises several structural layers, the inner two comprising a core, which assembles before addition of the outer proteins, VP2 and VP5. Two symmetric trimers of VP5 fit like pegs into two distinct pits on the core and undergo pH conformational changes in the context of the virus, associated with cell entry. Here we show that in isolation VP5 alone undergoes essentially the same changes with pH and confirm a helical transition, indicating that VP5 is a motor during cell entry. In the absence of VP5 the two pits on the core differ from each other, presumably due to the asymmetric underlying structure of VP3, the innermost capsid protein. On insertion of VP5 these pits become closely similar and remain similar at low pH whilst VP5 is present. This natural asymmetry presumably destabilises the attachment of VP5, facilitating ejection upon low pH, membrane penetration and cell entry.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diversifying selection identified in immune epitopes of bovine coronavirus isolates from Irish cattle. 从爱尔兰牛分离的牛冠状病毒免疫表位中发现的多样化选择。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002019
Tristan Russell, Jose Maria Lozano, Cailyn Challinor, Gerald Barry
{"title":"Diversifying selection identified in immune epitopes of bovine coronavirus isolates from Irish cattle.","authors":"Tristan Russell, Jose Maria Lozano, Cailyn Challinor, Gerald Barry","doi":"10.1099/jgv.0.002019","DOIUrl":"10.1099/jgv.0.002019","url":null,"abstract":"<p><p><i>Bovine betacoronavirus</i> (BoCoV) is a pneumoenteric pathogen of cattle that is closely related to human coronavirus OC43. Vaccines are administered to protect against diseases caused by BoCoV, but knowledge gaps exist with regard to correlates of protection and the effect of immune evasion on driving evolution. In this study, immune epitopes were mapped onto BoCoV structural proteins, including spike and haemagglutinin esterase (HE), and then supported with targeted gene sequencing of Irish clinical isolates and selective pressure analysis. Increased prevalence of diversifying selection and amino acid changes in some mapped immune epitopes suggests that immune escape is selecting for non-synonymous mutations arising in these regions. Selection analysis and sequencing provided increased support for neutralising antibody (nAb) epitopes compared to others, suggesting that nAbs are an important arm of the immune response to BoCoV. Phylogenetic analysis of spike and HE sequences showed that Irish isolates from this study were in the European clade, except for one HE sequence that sat in the Asian/American clade, while the spike gene of this sample was in the European clade. Recombination between a European and an Asian/American isolate would give rise to such a sequence. This study has gathered evidence suggesting that pressure to evade the nAb response is contributing to BoCoV evolution.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Porcine deltacoronavirus nucleocapsid protein interacts with the Grb2 through its proline-rich motifs to induce activation of the Raf-MEK-ERK signal pathway and promote virus replication. 猪 deltacoronavirus 核壳蛋白通过其富含脯氨酸的基序与 Grb2 相互作用,诱导 Raf-MEK-ERK 信号通路的激活并促进病毒复制。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002014
Mingxia Li, Liping Zhang, Peng Zhou, Zhongwang Zhang, Ruiming Yu, Yongguang Zhang, Yonglu Wang, Huichen Guo, Li Pan, Sa Xiao, Xinsheng Liu
{"title":"Porcine deltacoronavirus nucleocapsid protein interacts with the Grb2 through its proline-rich motifs to induce activation of the Raf-MEK-ERK signal pathway and promote virus replication.","authors":"Mingxia Li, Liping Zhang, Peng Zhou, Zhongwang Zhang, Ruiming Yu, Yongguang Zhang, Yonglu Wang, Huichen Guo, Li Pan, Sa Xiao, Xinsheng Liu","doi":"10.1099/jgv.0.002014","DOIUrl":"10.1099/jgv.0.002014","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV), an enteropathogenic coronavirus, causes severe watery diarrhoea, dehydration and high mortality in piglets, which has the potential for cross-species transmission in recent years. Growth factor receptor-bound protein 2 (Grb2) is a bridging protein that can couple cell surface receptors with intracellular signal transduction events. Here, we investigated the reciprocal regulation between Grb2 and PDCoV. It is found that Grb2 regulates PDCoV infection and promotes IFN-β production through activating Raf/MEK/ERK/STAT3 pathway signalling in PDCoV-infected swine testis cells to suppress viral replication. PDCoV N is capable of interacting with Grb2. The proline-rich motifs in the N- or C-terminal region of PDCoV N were critical for the interaction between PDCoV-N and Grb2. Except for <i>Deltacoronavirus</i> PDCoV N, the <i>Alphacoronavirus</i> PEDV N protein could interact with Grb2 and affect the regulation of PEDV replication, while the N protein of <i>Betacoronavirus</i> PHEV and <i>Gammacoronavirus</i> AIBV could not interact with Grb2. PDCoV N promotes Grb2 degradation by K48- and K63-linked ubiquitin-proteasome pathways. Overexpression of PDCoV N impaired the Grb2-mediated activated effect on the Raf/MEK/ERK/STAT3 signal pathway. Thus, our study reveals a novel mechanism of how host protein Grb2 protein regulates viral replication and how PDCoV N escaped natural immunity by interacting with Grb2.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Arginyltransferase 1 (ATE1)-mediated proteasomal degradation of viral haemagglutinin protein: a unique host defence mechanism. 精氨酰转移酶 1 (ATE1) 介导的蛋白酶体降解病毒血凝素蛋白:一种独特的宿主防御机制。
IF 3.6 4区 医学
Journal of General Virology Pub Date : 2024-08-01 DOI: 10.1099/jgv.0.002020
Kamal Shokeen, Malay Kumar Baroi, Manjeet Chahar, Debapratim Das, Harimohan Saini, Sachin Kumar
{"title":"Arginyltransferase 1 (ATE1)-mediated proteasomal degradation of viral haemagglutinin protein: a unique host defence mechanism.","authors":"Kamal Shokeen, Malay Kumar Baroi, Manjeet Chahar, Debapratim Das, Harimohan Saini, Sachin Kumar","doi":"10.1099/jgv.0.002020","DOIUrl":"10.1099/jgv.0.002020","url":null,"abstract":"<p><p>The extensive protein production in virus-infected cells can disrupt protein homeostasis and activate various proteolytic pathways. These pathways utilize post-translational modifications (PTMs) to drive the ubiquitin-mediated proteasomal degradation of surplus proteins. Protein arginylation is the least explored PTM facilitated by arginyltransferase 1 (ATE1) enzyme. Several studies have provided evidence supporting its importance in multiple physiological processes, including ageing, stress, nerve regeneration, actin formation and embryo development. However, its function in viral pathogenesis is still unexplored. The present work utilizes Newcastle disease virus (NDV) as a model to establish the role of the ATE1 enzyme and its activity in pathogenesis. Our data indicate a rise in levels of N-arginylated cellular proteins in the infected cells. Here, we also explore the haemagglutinin-neuraminidase (HN) protein of NDV as a presumable target for arginylation. The data indicate that the administration of Arg amplifies the arginylation process, resulting in reduced stability of the HN protein. ATE1 enzyme activity inhibition and gene expression knockdown studies were also conducted to analyse modulation in HN protein levels, which further substantiated the findings. Moreover, we also observed Arg addition and probable ubiquitin modification to the HN protein, indicating engagement of the proteasomal degradation machinery. Lastly, we concluded that the enhanced levels of the ATE1 enzyme could transfer the Arg residue to the N-terminus of the HN protein, ultimately driving its proteasomal degradation.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"105 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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