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Identification of a novel caspase cleavage motif AEAD 鉴定新型 Caspase 裂解基序 AEAD。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.001
Yujie Fang , Zhou Gong , Miaomiao You , Ke Peng
{"title":"Identification of a novel caspase cleavage motif AEAD","authors":"Yujie Fang ,&nbsp;Zhou Gong ,&nbsp;Miaomiao You ,&nbsp;Ke Peng","doi":"10.1016/j.virs.2024.08.001","DOIUrl":"10.1016/j.virs.2024.08.001","url":null,"abstract":"<div><div>Infections of many viruses induce caspase activation to regulate multiple cellular pathways, including programmed cell death, immune signaling and etc. Characterizations of caspase cleavage sites and substrates are important for understanding the regulation mechanisms of caspase activation. Here, we identified and analyzed a novel caspase cleavage motif AEAD, and confirmed its caspase dependent cleavage activity in natural substrate, such as nitric oxide-associated protein 1 (NOA1). Fusing the enhanced green fluorescent protein (EGFP) with the mitochondrial marker protein Tom20 through the AEAD motif peptide localized EGFP to the mitochondria. Upon the activation of caspase triggered by Sendai virus (SeV) or herpes simplex virus type 1 (HSV-1) infection, EGFP diffusely localized to the cell due to the caspase-mediated cleavage, thus allowing visual detection of the virus-induced caspase activation. An AEAD peptide-derived inhibitor Z-AEAD-FMK were developed, which significantly inhibited the activities of caspases-1, -3, -6, -7, -8 and -9, exhibiting a broad caspase inhibition effect. The inhibitor further prevented caspases-mediated cleavage of downstream substrates, including BID, PARP1, LMNA, pro-IL-1β, pro-IL-18, GSDMD and GSDME, protecting cells from virus-induced apoptotic and pyroptotic cell death. Together, our findings provide a new perspective for the identification of novel caspase cleavage motifs and the development of new caspase inhibitors and anti-inflammatory drugs.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 755-766"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 spatiotemporal analysis of SARS-CoV-2 transmission in China since the termination of the dynamic zero-COVID policy 自动态零COVID政策终止以来中国SARS-CoV-2传播的时空分析。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.003
Jiaying Li , Jingqi Yang , Xiao Ding , Hangyu Zhou , Na Han , Aiping Wu
{"title":"The spatiotemporal analysis of SARS-CoV-2 transmission in China since the termination of the dynamic zero-COVID policy","authors":"Jiaying Li ,&nbsp;Jingqi Yang ,&nbsp;Xiao Ding ,&nbsp;Hangyu Zhou ,&nbsp;Na Han ,&nbsp;Aiping Wu","doi":"10.1016/j.virs.2024.09.003","DOIUrl":"10.1016/j.virs.2024.09.003","url":null,"abstract":"<div><div>China's dynamic zero-COVID policy has effectively curbed the spread of SARS-CoV-2, while inadvertently creating immunity gaps within its population. Subsequent surges in COVID-19 cases linked to various SARS-CoV-2 lineages post-policy termination necessitate a thorough investigation into the epidemiological landscape. This study addresses this issue by analyzing a comprehensive dataset of 39,456 high-quality genomes collected nationwide over an 11-month period since policy termination. Through lineage assignment, phylogenetic analysis, pandemic pattern comparison, phylodynamic reconstruction, and recombination detection, we found that China's post-epidemic period could be divided into three stages, along with dynamic changes in dominant lineages. Geographical clustering of similar lineages implies the importance of cross-border cooperation among neighboring regions. Compared to the USA, UK, and Japan, China exhibits unique trajectories of lineage epidemics, characterized by initial lagging followed by subsequent advancement, indicating the potential influence of diverse prevention and control policies on lineage epidemic patterns. Hong Kong, Shanghai, and Hubei emerge as pivotal nodes in the nationwide spread, marking a shift in the transmission center from east to central regions of China. Although China hasn't experienced significant variant emergence, the detection and validation of the novel recombination event, XCN lineage, underscore the ongoing virus evolution. Overall, this study systematically analyzes the spatiotemporal transmission of SARS-CoV-2 virus in China since the termination of the dynamic zero-COVID policy, offering valuable insights for regional surveillance and evidence-based public health policymaking.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 737-746"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies Mpox 病毒独特的免疫规避机制及其对开发新型疫苗和免疫疗法的影响。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.008
Dong Fang , Yan Liu , Dou Dou , Bin Su
{"title":"The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies","authors":"Dong Fang ,&nbsp;Yan Liu ,&nbsp;Dou Dou ,&nbsp;Bin Su","doi":"10.1016/j.virs.2024.08.008","DOIUrl":"10.1016/j.virs.2024.08.008","url":null,"abstract":"<div><div>Mpox is an infectious and contagious zoonotic disease caused by the mpox virus (MPXV), which belongs to the genus <em>Orthopoxvirus</em>. Since 2022, MPXV has posed a significant threat to global public health. The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency. The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system. Specifically, MPXV employs unique immune evasion strategies against a wide range of immunological elements, presenting a considerable challenge for treatment, especially following the discontinuation of routine smallpox vaccination among the general population. In this review, we start by discussing the entry of the mpox virus and the onset of early infection, followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses. Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection. With respect to adaptive immunity, mpox viruses exhibit unique and exceptional T-cell inhibition capabilities, thereby comprehensively remodeling the host immune environment. The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system. The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating. Finally, we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development. This review may provide valuable information for the development of new immunological treatments for mpox.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 709-718"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants 三价 SARS-CoV-2 病毒样颗粒疫苗对 XBB.1 和 BA.2.86 变体具有广谱中和和保护作用。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.005
Lu Zhang , Siyu Tian , Jun Dai , Yuanyuan Li , Yu Zhou , Yan Li , Jiao Xu , Shuyun Liu , Zhiwei Lin , Zhaoyong Zhang , Jiantao Chen , Peilan Wei , Jingxian Zhao , Jing Jin , Yanqun Wang , Jincun Zhao
{"title":"Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants","authors":"Lu Zhang ,&nbsp;Siyu Tian ,&nbsp;Jun Dai ,&nbsp;Yuanyuan Li ,&nbsp;Yu Zhou ,&nbsp;Yan Li ,&nbsp;Jiao Xu ,&nbsp;Shuyun Liu ,&nbsp;Zhiwei Lin ,&nbsp;Zhaoyong Zhang ,&nbsp;Jiantao Chen ,&nbsp;Peilan Wei ,&nbsp;Jingxian Zhao ,&nbsp;Jing Jin ,&nbsp;Yanqun Wang ,&nbsp;Jincun Zhao","doi":"10.1016/j.virs.2024.08.005","DOIUrl":"10.1016/j.virs.2024.08.005","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 836-839"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Antiviral activity of vitamin D derivatives against severe fever with thrombocytopenia syndrome virus in vitro and in vivo 维生素 D 衍生物在体外和体内对严重发热伴血小板减少综合征病毒的抗病毒活性。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.007
Chongda Luo , Xintong Yan , Shaokang Yang , Sichen Ren , Yan Luo , Jiazheng Li , Ping Wang , Yunfeng Shao , Wei Li , Song Li , Jingjing Yang , Ruiyuan Cao , Wu Zhong
{"title":"Antiviral activity of vitamin D derivatives against severe fever with thrombocytopenia syndrome virus in vitro and in vivo","authors":"Chongda Luo ,&nbsp;Xintong Yan ,&nbsp;Shaokang Yang ,&nbsp;Sichen Ren ,&nbsp;Yan Luo ,&nbsp;Jiazheng Li ,&nbsp;Ping Wang ,&nbsp;Yunfeng Shao ,&nbsp;Wei Li ,&nbsp;Song Li ,&nbsp;Jingjing Yang ,&nbsp;Ruiyuan Cao ,&nbsp;Wu Zhong","doi":"10.1016/j.virs.2024.08.007","DOIUrl":"10.1016/j.virs.2024.08.007","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both <em>in vitro</em> and <em>in vivo</em>. An <em>in vitro</em> study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dose-dependent manner. Subsequently, <em>in vivo</em> studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, <em>in vitro</em> and <em>in vivo</em> drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 802-811"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Single-cell RNA-sequencing reveals a profound immune cell response in human cytomegalovirus-infected humanized mice 单细胞 RNA 序列分析揭示了人巨细胞病毒感染人源化小鼠体内免疫细胞的深刻反应。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.006
An Wang , Xiao-Xu Zhu , Yuanyuan Bie , Bowen Zhang , Wenting Ji , Jing Lou , Muhan Huang , Xi Zhou , Yujie Ren
{"title":"Single-cell RNA-sequencing reveals a profound immune cell response in human cytomegalovirus-infected humanized mice","authors":"An Wang ,&nbsp;Xiao-Xu Zhu ,&nbsp;Yuanyuan Bie ,&nbsp;Bowen Zhang ,&nbsp;Wenting Ji ,&nbsp;Jing Lou ,&nbsp;Muhan Huang ,&nbsp;Xi Zhou ,&nbsp;Yujie Ren","doi":"10.1016/j.virs.2024.08.006","DOIUrl":"10.1016/j.virs.2024.08.006","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) is a common herpesvirus that persistently infects a large portion of the world's population. Despite the robust host immune response, HCMV is able to replicate, evade host defenses, and establish latency throughout the lifespan by developing multiple immunomodulatory strategies, making the studies on the interaction between HCMV infection and host response particularly important. HCMV has a strict host specificity that specifically infects humans. Therefore, most of the <em>in vivo</em> researches of HCMV rely on clinical samples. Fortunately, the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection. Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells. In this study, we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice, which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 782-792"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
A bivalent Delta/BA.5 mRNA vaccine elicits broad immune responses against various lineages of SARS-CoV-2 including JN.1 二价 Delta/BA.5 mRNA 疫苗可针对包括 JN.1 在内的多种 SARS-CoV-2 株系引起广泛的免疫反应。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.08.003
Kangyin Li , Qi Liu , Yan Wu , Bihao Wu , Shaohong Chen , Xinghai Zhang , Xiaoying Jia , Rui Gong , Yucai Peng , Huajun Zhang , Sandra Chiu
{"title":"A bivalent Delta/BA.5 mRNA vaccine elicits broad immune responses against various lineages of SARS-CoV-2 including JN.1","authors":"Kangyin Li ,&nbsp;Qi Liu ,&nbsp;Yan Wu ,&nbsp;Bihao Wu ,&nbsp;Shaohong Chen ,&nbsp;Xinghai Zhang ,&nbsp;Xiaoying Jia ,&nbsp;Rui Gong ,&nbsp;Yucai Peng ,&nbsp;Huajun Zhang ,&nbsp;Sandra Chiu","doi":"10.1016/j.virs.2024.08.003","DOIUrl":"10.1016/j.virs.2024.08.003","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 833-835"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017–2021 2017-2021 年中国急性下呼吸道感染患儿呼吸道合胞病毒融合蛋白基因变异多中心研究。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.002
Yiliang Fu , Fei Li , Yun Zhu , Luci Huang , Qiuping Li , Hanwen Zhang , Lili Zhong , Hailin Zhang , Zheng-xiu Luo , Gen Lu , Jikui Deng , Lingfeng Cao , Ying Wu , Rong Jin , Lei Li , Lili Xu , Xiangpeng Chen , Zhengde Xie
{"title":"A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017–2021","authors":"Yiliang Fu ,&nbsp;Fei Li ,&nbsp;Yun Zhu ,&nbsp;Luci Huang ,&nbsp;Qiuping Li ,&nbsp;Hanwen Zhang ,&nbsp;Lili Zhong ,&nbsp;Hailin Zhang ,&nbsp;Zheng-xiu Luo ,&nbsp;Gen Lu ,&nbsp;Jikui Deng ,&nbsp;Lingfeng Cao ,&nbsp;Ying Wu ,&nbsp;Rong Jin ,&nbsp;Lei Li ,&nbsp;Lili Xu ,&nbsp;Xiangpeng Chen ,&nbsp;Zhengde Xie","doi":"10.1016/j.virs.2024.09.002","DOIUrl":"10.1016/j.virs.2024.09.002","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (ALRTI) in children under five years of age. Between 2017 and 2021, 396 complete sequences of the RSV <em>F</em> gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China. In addition, 151 sequences from China were sourced from GenBank and GISAID, making a total of 549 RSV <em>F</em> gene sequences subjected to analysis. Phylogenetic and genetic diversity analyses revealed that the RSV <em>F</em> genes circulating in China from 2017 to 2021 have remained relatively conserved, although some amino acids (AAs) have undergone changes. AA mutations with frequencies ≥ 10% were identified at six sites and the p27 region: V384I (site I), N276S (site II), R213S (site Ø), and K124N (p27) for RSV A; F45L (site I), M152I/L172Q/S173 ​L/I185V/K191R (site V), and R202Q/I206M/Q209R (site Ø) for RSV B. Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A, while the K191R, I206M, and Q209R frequencies increased by over 10% in RSV B. Notably, the nirsevimab-resistant mutation, S211N in RSV B, increased in frequency from 0% to 1.15%. Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations, with low root-mean-square deviation values. These results could provide foundational data from China for the development of RSV mAbs and vaccines.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 727-736"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Issue Cover 发行封面
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/S1995-820X(24)00153-6
{"title":"Issue Cover","authors":"","doi":"10.1016/S1995-820X(24)00153-6","DOIUrl":"10.1016/S1995-820X(24)00153-6","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Page OFC"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71 合理设计 DNA 发射的人类肠道病毒 71 型减毒活疫苗。
IF 5.5 3区 医学
Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/j.virs.2024.09.008
Rong-Rong Zhang , Meng-Jiao He , Chao Zhou , Yan-Peng Xu , Wei Tang , Tian-Shu Cao , Zheng-Jian Wang , Mei Wu , Tao Ming , Yi-Jiao Huang , Meng-Xu Sun , Hui Zhao , Yong-Qiang Deng , Xiao-Feng Li , Bin Wang , Qing Ye , Cheng-Feng Qin
{"title":"Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71","authors":"Rong-Rong Zhang ,&nbsp;Meng-Jiao He ,&nbsp;Chao Zhou ,&nbsp;Yan-Peng Xu ,&nbsp;Wei Tang ,&nbsp;Tian-Shu Cao ,&nbsp;Zheng-Jian Wang ,&nbsp;Mei Wu ,&nbsp;Tao Ming ,&nbsp;Yi-Jiao Huang ,&nbsp;Meng-Xu Sun ,&nbsp;Hui Zhao ,&nbsp;Yong-Qiang Deng ,&nbsp;Xiao-Feng Li ,&nbsp;Bin Wang ,&nbsp;Qing Ye ,&nbsp;Cheng-Feng Qin","doi":"10.1016/j.virs.2024.09.008","DOIUrl":"10.1016/j.virs.2024.09.008","url":null,"abstract":"<div><div>Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. <em>In vitro</em> and <em>in vivo</em> transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR<sup>−/−</sup> mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 ​μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 812-820"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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