Virologica Sinica最新文献

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Development and immunoprotection assessment of novel vaccines for avian infectious bronchitis virus 禽传染性支气管炎病毒新型疫苗的研制及免疫保护效果评价。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.03.008
Benli Huang , Sheng Chen , Zhanxin Wang , Keyu Feng , Yutao Teng , Ruoying Li , Guanming Shao , Jiaqian Rao , Xinheng Zhang , Qingmei Xie
{"title":"Development and immunoprotection assessment of novel vaccines for avian infectious bronchitis virus","authors":"Benli Huang ,&nbsp;Sheng Chen ,&nbsp;Zhanxin Wang ,&nbsp;Keyu Feng ,&nbsp;Yutao Teng ,&nbsp;Ruoying Li ,&nbsp;Guanming Shao ,&nbsp;Jiaqian Rao ,&nbsp;Xinheng Zhang ,&nbsp;Qingmei Xie","doi":"10.1016/j.virs.2025.03.008","DOIUrl":"10.1016/j.virs.2025.03.008","url":null,"abstract":"<div><div>Infectious bronchitis (IB), a highly contagious acute respiratory disease affecting avian species, poses significant challenges to poultry production. The causative agent, infectious bronchitis virus (IBV), exhibits a high mutation rate, leading to limited cross-protection by existing vaccines. This necessitates the development of novel vaccines. This study, based on preliminary investigations conducted by our research team, identified six potential strains (PYG QX1, ZQF QX2, FQH QX3, LYZ QX4, XXX QX5, and CSL strains) for vaccine development. Previous pathogenicity test and serum cross-neutralization experiments conducted in this study have demonstrated that the FQH QX3 strain exhibited the weakest pathogenicity and the broadest spectrum of serum neutralization, while the CSL strain showed the highest pathogenicity and was the most challenging to neutralize, posing the greatest difficulty in prevention and control. Subsequently, we constructed and rescued recombinant vaccine candidates, H120-FQH QX3, and H120-CSL, expressing the S1 and N proteins of the FQH QX3 and CSL strains, respectively. Immunization protection experiments indicated that the H120-CSL recombinant vaccine candidate exhibited the most effective immune protection, making it a promising candidate for further study and evaluation as a recombinant vaccine. The <em>S1</em> and <em>N</em> genes of the CSL strain demonstrated strong immunogenicity, making them potential candidate antigen genes for future vaccine development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 462-476"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus 利巴韦林和沙粒病毒进入抑制剂LHF-535联合使用可增强对真正拉沙病毒的抗病毒作用。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.003
Cheng Peng , Jialing Hu , Yuan Bai , Wei Wu , Wenting Mao , Yang Liu , Yi Wan , Lei Zhang , Wei Li , Tingting Tian , Tiezhu Liu , Yanhai Wang , Mifang Liang , Jun Han , Zhiming Yuan , Jiandong Li , Chao Shan , Fei Deng , Wei Wang
{"title":"Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus","authors":"Cheng Peng ,&nbsp;Jialing Hu ,&nbsp;Yuan Bai ,&nbsp;Wei Wu ,&nbsp;Wenting Mao ,&nbsp;Yang Liu ,&nbsp;Yi Wan ,&nbsp;Lei Zhang ,&nbsp;Wei Li ,&nbsp;Tingting Tian ,&nbsp;Tiezhu Liu ,&nbsp;Yanhai Wang ,&nbsp;Mifang Liang ,&nbsp;Jun Han ,&nbsp;Zhiming Yuan ,&nbsp;Jiandong Li ,&nbsp;Chao Shan ,&nbsp;Fei Deng ,&nbsp;Wei Wang","doi":"10.1016/j.virs.2025.04.003","DOIUrl":"10.1016/j.virs.2025.04.003","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 491-494"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro 氯法齐明靶向刺突蛋白和RdRp对猪流行性腹泻病毒表现出高效的体外抗病毒活性。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.012
Shuting Zhou , Junrui Zhu , Houde Zhao , Zixin Huang , Kangqi Zheng , Fan Xia , Yufan Xu , Guocheng Zhao , Jijie Jiang , En Zhang , Haoyang Nian , Li Cui , Tao Sun , Xiangfeng Wang , Yanjun Zhou , Zhibiao Yang , Zhe Wang
{"title":"Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro","authors":"Shuting Zhou ,&nbsp;Junrui Zhu ,&nbsp;Houde Zhao ,&nbsp;Zixin Huang ,&nbsp;Kangqi Zheng ,&nbsp;Fan Xia ,&nbsp;Yufan Xu ,&nbsp;Guocheng Zhao ,&nbsp;Jijie Jiang ,&nbsp;En Zhang ,&nbsp;Haoyang Nian ,&nbsp;Li Cui ,&nbsp;Tao Sun ,&nbsp;Xiangfeng Wang ,&nbsp;Yanjun Zhou ,&nbsp;Zhibiao Yang ,&nbsp;Zhe Wang","doi":"10.1016/j.virs.2025.05.012","DOIUrl":"10.1016/j.virs.2025.05.012","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) infection causes acute watery diarrhea in neonatal piglets, leading to substantial economic losses within the pig farming industry. This study demonstrates that clofazimine (CFZ) significantly inhibits PEDV replication in a dose-dependent manner <em>in vitro</em>, with negligible cytotoxicity. Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle. Using a CoV-RdRp-Gluc reporter system, we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase (RdRp), and determined a low IC<sub>50</sub> value of 0.1364 ​μM. Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV. Transcriptome analysis of Vero E6 cells, with and without CFZ treatment, revealed a significant change in transcriptional activity at 8 ​h post-infection (hpi). Moreover, the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ <em>in vitro</em>. Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 477-490"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights into cross-species infection: Porcine epidemic diarrhea virus infections in the rodent 冠状病毒跨物种感染的认识:猪流行性腹泻病毒在啮齿动物中的感染。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.03.012
Jianing Chen , Zemei Wang , Shengyu Lin , Mengling Gao , Yongheng Shao , Shuxian Li , Qingbo Chen , Yaru Cui , Yonghao Hu , Guangliang Liu
{"title":"Insights into cross-species infection: Porcine epidemic diarrhea virus infections in the rodent","authors":"Jianing Chen ,&nbsp;Zemei Wang ,&nbsp;Shengyu Lin ,&nbsp;Mengling Gao ,&nbsp;Yongheng Shao ,&nbsp;Shuxian Li ,&nbsp;Qingbo Chen ,&nbsp;Yaru Cui ,&nbsp;Yonghao Hu ,&nbsp;Guangliang Liu","doi":"10.1016/j.virs.2025.03.012","DOIUrl":"10.1016/j.virs.2025.03.012","url":null,"abstract":"<div><div>The cross-species infection of coronaviruses has resulted in several major epidemics since 2003. Porcine epidemic diarrhea virus (PEDV) is a devastating swine enteric coronavirus, which targets pigs as the only natural reservoir. In this study, the nucleic acid of PEDV was detected in rat fecal samples collected from pig farms. Further animal tests showed that PEDV can cause systemic infections in neonatal mice and rats via intracranial inoculation. The brain, lung, intestine and spleen were all targets for PEDV in rodents in contrast to the intestine being targeted in pigs. Morbidity and mortality vary via different infection routes. PEDV was also detectable in feces after infection, suggesting that the infected rodents were potential infectious sources. Moreover, the cerebral tropism of PEDV was verified in piglets via orally inoculation, which had not been identified before. In conclusion, our findings demonstrate that PEDV could cross the species barrier to infect mice and rats through different routes in experimental settings. Although it is highly devastating to piglets, PEDV changes the target organs and turns to be milder when meeting with new hosts. Based on these findings, more attention should be paid to the potential cross-species infection of PEDV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 301-313"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A mouse model of Crimean-Congo hemorrhagic fever virus-induced coagulopathy 克里米亚-刚果出血热病毒致凝血病小鼠模型。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.04.008
Hui Zhang , Ziyang Jiang , Haidang Liao , Jiang Li , Manli Wang , Yiwu Zhou , Zhihong Hu , Jia Liu
{"title":"A mouse model of Crimean-Congo hemorrhagic fever virus-induced coagulopathy","authors":"Hui Zhang ,&nbsp;Ziyang Jiang ,&nbsp;Haidang Liao ,&nbsp;Jiang Li ,&nbsp;Manli Wang ,&nbsp;Yiwu Zhou ,&nbsp;Zhihong Hu ,&nbsp;Jia Liu","doi":"10.1016/j.virs.2025.04.008","DOIUrl":"10.1016/j.virs.2025.04.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 499-502"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Compromised efferocytosis during aging is related to COVID-19 severity in mice 衰老过程中红细胞减少与小鼠COVID-19严重程度有关。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.008
Xianliang Ke , Xian Lin , Jin Wang , Minqi Chen , Xiaoqin Jian , Chang Ye , Quanjiao Chen
{"title":"Compromised efferocytosis during aging is related to COVID-19 severity in mice","authors":"Xianliang Ke ,&nbsp;Xian Lin ,&nbsp;Jin Wang ,&nbsp;Minqi Chen ,&nbsp;Xiaoqin Jian ,&nbsp;Chang Ye ,&nbsp;Quanjiao Chen","doi":"10.1016/j.virs.2025.05.008","DOIUrl":"10.1016/j.virs.2025.05.008","url":null,"abstract":"<div><div>Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019 (COVID-19). In older individuals, a dysregulated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contributes to disease severity; however, the underlying mechanism remains elusive. In this study, we established an aging mouse model of COVID-19, successfully replicating the development of a relatively severe disease in older adults. Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs, accompanied by an over-activated inflammatory response, especially in aging mice. Compared to young mice, aging mice showed extensive neutrophil activation, NETosis, and a dramatic decrease in the number of alveolar macrophages (AMs). Moreover, as important executors of efferocytosis, AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice. Further analysis indicated that the efferocytosis of neutrophils, whether undergoing apoptosis or NETosis, was compromised after SARS-CoV-2 infection. Since efferocytosis is a key process in inflammatory resolution, impaired efferocytosis may contribute to hyperinflammation in aging lungs. Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 419-429"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eltrombopag, an FDA-approved drug, inhibits dengue virus type 2 by targeting NS2B-NS3 protease Eltrombopag是一种fda批准的药物,通过靶向NS2B-NS3蛋白酶抑制登革热病毒2型。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-06-01 DOI: 10.1016/j.virs.2025.05.009
Xuerui Zhu , Xiao Gao , Yan Wu , Jia Lu , Xinlan Chen , Chenshu Zhao , Haoyu Li , Zhongfa Zhang , Shuwen Liu , Gengfu Xiao , Xiaoyan Pan
{"title":"Eltrombopag, an FDA-approved drug, inhibits dengue virus type 2 by targeting NS2B-NS3 protease","authors":"Xuerui Zhu ,&nbsp;Xiao Gao ,&nbsp;Yan Wu ,&nbsp;Jia Lu ,&nbsp;Xinlan Chen ,&nbsp;Chenshu Zhao ,&nbsp;Haoyu Li ,&nbsp;Zhongfa Zhang ,&nbsp;Shuwen Liu ,&nbsp;Gengfu Xiao ,&nbsp;Xiaoyan Pan","doi":"10.1016/j.virs.2025.05.009","DOIUrl":"10.1016/j.virs.2025.05.009","url":null,"abstract":"<div><div>Dengue viruses (DENV) have spread throughout the world and pose a huge threat to human life. The most widespread serotype is type 2 DENV (DENV 2), which has no specific treatment. NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein; thus, it is considered a promising target for antiviral discovery. In this study, we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library. Eltrombopag was screened out of 3273 drugs, and demonstrated inhibition on DENV 2 ​at the micromolar level <em>in vitro,</em> significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection. Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible, non-competitive manner, therefore inhibiting DENV 2 ​at the post-infection stage. In addition, eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus, suggesting its potential as a broad-spectrum antiviral agent. This study repurposed eltrombopag as a promising antiviral agent against DENV, providing an alternative for antiviral development against flaviviruses.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 3","pages":"Pages 439-450"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
WITHDRAWN: Comparative metatranscriptome analysis in gut reveals insignificant host or microbiota changes in SARS-related coronavirus naturally infected bats. 撤回:肠道的比较转录组分析显示,在sars相关冠状病毒自然感染的蝙蝠中,宿主或微生物群的变化微不足道。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-04-07 DOI: 10.1016/j.virs.2025.04.002
Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou
{"title":"WITHDRAWN: Comparative metatranscriptome analysis in gut reveals insignificant host or microbiota changes in SARS-related coronavirus naturally infected bats.","authors":"Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou","doi":"10.1016/j.virs.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.002","url":null,"abstract":"<p><p>The publisher regrets that this article has withdrawn.\u0000The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The SARS-CoV-2 NSP4 T492I mutation promotes double-membrane vesicle formation to facilitate transmission SARS-CoV-2 NSP4 T492I 突变促进了双膜囊泡的形成,从而有利于传播。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-04-01 DOI: 10.1016/j.virs.2025.03.010
Pei Wang , Buyun Tian , Ke Xiao , Wei Ji , Zonghong Li
{"title":"The SARS-CoV-2 NSP4 T492I mutation promotes double-membrane vesicle formation to facilitate transmission","authors":"Pei Wang ,&nbsp;Buyun Tian ,&nbsp;Ke Xiao ,&nbsp;Wei Ji ,&nbsp;Zonghong Li","doi":"10.1016/j.virs.2025.03.010","DOIUrl":"10.1016/j.virs.2025.03.010","url":null,"abstract":"<div><div>The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in mutations not only in the spike protein, aiding immune evasion, but also in the NSP3/4/6 proteins, crucial for regulating double-membrane vesicle (DMV) formation. However, the functional consequences of these NSP3/4/6 mutations remain poorly understood. In this study, a systematic analysis was conducted to investigate the evolutionary patterns of NSP3/4/6 mutations and their impact on DMV formation. The findings revealed that the NSP4 T492I mutation, a prevalent mutation found in all Delta and Omicron sub-lineages, notably enhances DMV formation. Mechanistically, the NSP4 T492I mutation enhances its homodimerization, leading to an increase in the size of puncta induced by NSP3/4, and also augments endoplasmic reticulum (ER) membrane curvature, resulting in a higher DMV density per fluorescent puncta. This study underscores the significance of the NSP4 T492I mutation in modulating DMV formation, with potential implications for the transmission dynamics of SARS-CoV-2. It contributes valuable insights into how these mutations impact viral replication and pathogenesis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 2","pages":"Pages 225-235"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure-function insights into the dual role of African swine fever virus pB318L: A typical geranylgeranyl-diphosphate synthase and a nuclear import protein 非洲猪瘟病毒pB318L的结构-功能双重作用:一种典型的香叶二磷酸合成酶和一种核输入蛋白。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2025-04-01 DOI: 10.1016/j.virs.2025.03.013
Hai-Fan Zhao , Ying Wang , Xiao-Hong Liu , Xian-Hui Liu , Zhi Geng , Zeng-Qiang Gao , Li Huang , Chang-Jiang Weng , Yu-Hui Dong , Heng Zhang
{"title":"Structure-function insights into the dual role of African swine fever virus pB318L: A typical geranylgeranyl-diphosphate synthase and a nuclear import protein","authors":"Hai-Fan Zhao ,&nbsp;Ying Wang ,&nbsp;Xiao-Hong Liu ,&nbsp;Xian-Hui Liu ,&nbsp;Zhi Geng ,&nbsp;Zeng-Qiang Gao ,&nbsp;Li Huang ,&nbsp;Chang-Jiang Weng ,&nbsp;Yu-Hui Dong ,&nbsp;Heng Zhang","doi":"10.1016/j.virs.2025.03.013","DOIUrl":"10.1016/j.virs.2025.03.013","url":null,"abstract":"<div><div>African swine fever virus (ASFV) pB318L is an important protein for viral replication that acts as a membrane-bound <em>trans</em>-geranylgeranyl-diphosphate synthase (GGPPS) catalyzing the condensation of isopentenyl diphosphate (IPP) with allylic diphosphates. Recently we solved the crystal structure pB318L lacking N-terminal transmembrane region and performed a preliminary structural analysis. In this study, structure-based mutagenesis study and geranylgeranyl pyrophosphate (GGPP) production assay further revealed the key residues for the GGPPS activity. Structural comparison showed pB318L displays a strong similarity to typical GGPPSs instead of protein prenyltransferases. The phylogenetic analysis indicated pB318L may share a common ancestor with the GGPPSs from <em>Brassicaceae</em> plants rather than from its natural host. The subcellular localization analysis showed pB318L is localized in both nucleus and cytoplasm (including the endoplasmic reticulum membrane and mitochondria outer membrane). A unique N-terminal nuclear localization signal (NLS) following the transmembrane region was discovered in pB318L and the NLS was confirmed to be required for the nuclear import. We further revealed the NLS plays an essential role in the interaction with nuclear transporter karyopherin subunit alpha 1 (KPNA1). Their interaction may suppress signal transducers and activators of transcription 1 (STAT1) translocation and subsequently competitively inhibit nuclear import of IFN-stimulated gene factor 3 (ISGF3) complex. Our biochemical, structural and cellular analyses provide novel insights to pB318L that acts as an essential GGPPS that promotes viral replication and as a nuclear import protein that may be involved in immune evasion of ASFV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 2","pages":"Pages 236-246"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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