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IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-10-01 DOI: 10.1016/S1995-820X(24)00153-6

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 , 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","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":null,"pages":null},"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

Efficient and robust reverse genetics system for bovine rotavirus generation and its application for antiviral screening. 用于生成牛轮状病毒的高效、稳健的反向遗传学系统及其在抗病毒筛选中的应用。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-09-29 DOI: 10.1016/j.virs.2024.09.010

Song-Kang Qin, Kuan-Hao Li, Ben-Jin Liu, Cun Cao, De-Bin Yu, Zhi-Gang Jiang, Jun Wang, Yu-Xin Han, Fang Wang, Ying-Lin Qi, Chao Sun, Li Yu, Ji-Tao Chang, Xin Yin

{"title":"Efficient and robust reverse genetics system for bovine rotavirus generation and its application for antiviral screening.","authors":"Song-Kang Qin, Kuan-Hao Li, Ben-Jin Liu, Cun Cao, De-Bin Yu, Zhi-Gang Jiang, Jun Wang, Yu-Xin Han, Fang Wang, Ying-Lin Qi, Chao Sun, Li Yu, Ji-Tao Chang, Xin Yin","doi":"10.1016/j.virs.2024.09.010","DOIUrl":"10.1016/j.virs.2024.09.010","url":null,"abstract":"<p><p>Unveiling the molecular mechanisms underlying rotavirus replication and pathogenesis has been hampered by the lack of a reverse genetics (RG) system in the past. Since 2017, multiple plasmid-based RG systems for simian, human, and murine-like rotaviruses have been established. However, none of the described methods have supported the recovery of bovine rotaviruses (BRVs). Here, we established an optimized plasmid-based RG system for BRV culture-adapted strain (BRV G10P [15] BLR) and clinical isolates (BRV G6P [1] C73, G10P [11] HM26) based on a BHK-T7 cell clone stably expressing T7 polymerase. Furthermore, using this optimized RG system, we successfully rescued the reporter virus BRV rC73/Zs, rHM26/Zs and rBLR/Zs, harboring a genetically modified 1.8-kb segment 7 encoding full-length nonstructural protein 3 (NSP3) fused to ZsGreen, a 232-amino acid green fluorescent protein. Analysis of the stability of genomic insertions showed that the rC73/Zs and rBLR/Zs replicated efficiently and were genetically stable in seven rounds of serial passaging, while rHM26/Zs can be stabilized only up to the third generation, indicating that the BRV segment composition may influence the viral fitness. In addition, we adopted the recombinant reporter viruses for high-throughput screening application and discovered 12 candidates out of 1440 compounds with potential antiviral activities against rotavirus. In summary, this improved RG system of BRVs represents an important tool with great potential for understanding the molecular biology of BRV and facilitates the development of novel therapeutics and vaccines for BRV.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354981","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 G3P[3] bat rotavirus can infect cultured human cholangiocytes and cause biliary atresia symptom in suckling mice. G3P[3]蝙蝠轮状病毒可感染培养的人类胆管细胞，并导致乳鼠出现胆道闭锁症状。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-09-24 DOI: 10.1016/j.virs.2024.09.009

Pengfei Hao, Zhaoxia Pang, Qiaoqiao Qu, Chunmei Cui, Yuhang Jiang, Jing Chen, Zihan Gao, Zhiqiang Xu, Letian Li, Ningyi Jin, Chang Li

引用次数: 0

Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters. 基于铁蛋白纳米颗粒的尼帕病毒糖蛋白疫苗可在小鼠和仓鼠体内引起有效的保护性免疫反应。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-09-16 DOI: 10.1016/j.virs.2024.09.005

Shaohong Chen,Xinghai Zhang,Yanfeng Yao,Shengdong Wang,Kangyin Li,Baoyue Zhang,Tianxi Ye,Li Chen,Yan Wu,Entao Li,Bichao Xu,Pei Zhang,Xia Chuai,Yong Ran,Rui Gong,Huajun Zhang,Sandra Chiu

{"title":"Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters.","authors":"Shaohong Chen,Xinghai Zhang,Yanfeng Yao,Shengdong Wang,Kangyin Li,Baoyue Zhang,Tianxi Ye,Li Chen,Yan Wu,Entao Li,Bichao Xu,Pei Zhang,Xia Chuai,Yong Ran,Rui Gong,Huajun Zhang,Sandra Chiu","doi":"10.1016/j.virs.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.virs.2024.09.005","url":null,"abstract":"Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and Ghead (residues 182-602, FeNP-Ghead) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-Ghead, respectively) through Spycatcher/Spytag technology. Compared with sG and Ghead alone, FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group. These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 μg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257547","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

Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy. 双苄基异喹啉生物碱通过影响内溶酶体转运和自噬抑制黄病毒的进入和复制。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-09-07 DOI: 10.1016/j.virs.2024.09.001

Lihong Huang,Lele Liu,Junhai Zhu,Nanjun Chen,Jie Chen,Chuen-Fuk Chan,Fei Gao,Youqin Yin,Jiufeng Sun,Rongxin Zhang,Kehui Zhang,Wenbao Qi,Jianbo Yue

{"title":"Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy.","authors":"Lihong Huang,Lele Liu,Junhai Zhu,Nanjun Chen,Jie Chen,Chuen-Fuk Chan,Fei Gao,Youqin Yin,Jiufeng Sun,Rongxin Zhang,Kehui Zhang,Wenbao Qi,Jianbo Yue","doi":"10.1016/j.virs.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.virs.2024.09.001","url":null,"abstract":"Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), represent a substantial public health challenge as there are currently no approved treatments available. Here, we investigated the antiviral effects of bis-benzylisoquinoline alkaloids (BBAs) on flavivirus infections. We evaluated five specific BBAs-berbamine, tetrandrine, iso-tetrandrine, fangchinoline, and cepharanthine-and found that they effectively inhibited infections by ZIKV, DENV, or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle. Furthermore, we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes, causing lysosomal pH alkalization. Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels, leading to lysosomal dysfunction and reducing the expression of NCAM1, a key receptor for the entry of ZIKV into cells, thereby decreasing cells susceptibility to ZIKV infection. Additionally, BBAs inhibited the fusion of autophagosomes and lysosomes, significantly reducing viral RNA replication. Collectively, our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy, respectively, underscoring the potential of BBAs as therapeutic agents against flavivirus infections.","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180133","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

Antigenic analysis of the influenza B virus hemagglutinin protein. 乙型流感病毒血凝素蛋白的抗原分析。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-09-02 DOI: 10.1016/j.virs.2024.08.012

Mengyi Zhang, Chaoying Yang, Xi Wu, Yifei Wang, Lijie Wang, Qianqian Cui, Jincheng Tong, Yimeng An, Meina Cai, Shishi Cheng, Qi Jiang, Yulin Wang, Chenyan Zhao, Youchun Wang, Weijin Huang

{"title":"Antigenic analysis of the influenza B virus hemagglutinin protein.","authors":"Mengyi Zhang, Chaoying Yang, Xi Wu, Yifei Wang, Lijie Wang, Qianqian Cui, Jincheng Tong, Yimeng An, Meina Cai, Shishi Cheng, Qi Jiang, Yulin Wang, Chenyan Zhao, Youchun Wang, Weijin Huang","doi":"10.1016/j.virs.2024.08.012","DOIUrl":"10.1016/j.virs.2024.08.012","url":null,"abstract":"<p><p>Influenza B viruses (IBVs) primarily infect humans and are a common cause of respiratory infections in humans. Here, to systematically analyze the antigenicity of the IBVs Hemagglutinin (HA) protein, 31 B/Victoria and 19 B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data (GISAID), and pseudotyped viruses were constructed with the vesicular stomatitis virus system. Guinea pigs were immunized with three doses of vaccines (one dose of DNA vaccines following two doses of pseudotyped virus vaccines) of the seven IBV vaccine strains, and neutralizing antibodies against the pseudotyped viruses were tested. By comparing differences between various vaccine strains, we constructed several pseudotyped viruses that contained various mutations based on vaccine strain BV-21. The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year, with neutralization titers ranging from 370 to 840, while the level of neutralization against viruses prevalent in previous years decreased 1-10-fold. Each of the high-frequency epidemic strains of B/Victoria and B/Yamagata not only induced high neutralizing titers, but also had broadly neutralizing effects against virus strains of different years, with neutralizing titers ranging from 1000 to 7200. R141G, D197 N, and R203K were identified as affecting the antigenicity of IBV. These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133919","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

Bibliometric analysis of virology advancements in the 21st century. 21 世纪病毒学进展的文献计量分析。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-08-23 DOI: 10.1016/j.virs.2024.08.009

Lili Ma, Wei Pan, Jiali Si

引用次数: 0

Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain. 利用甲型肝炎病毒减毒活疫苗 H2 株的反向遗传系统鉴定参与细胞适应的病毒蛋白变异。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-08-14 DOI: 10.1016/j.virs.2024.08.004

Xiu-Li Yan, Jian Li, Qing-Qing Ma, Hong-Jiang Wang, Lin Li, Hui Zhao, Cheng-Feng Qin, Xiao-Feng Li

{"title":"Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain.","authors":"Xiu-Li Yan, Jian Li, Qing-Qing Ma, Hong-Jiang Wang, Lin Li, Hui Zhao, Cheng-Feng Qin, Xiao-Feng Li","doi":"10.1016/j.virs.2024.08.004","DOIUrl":"10.1016/j.virs.2024.08.004","url":null,"abstract":"<p><p>The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild-type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1<sup>-/-</sup> C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996602","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

Transmission restriction and genomic evolution co-shape the genetic diversity patterns of influenza A virus 传播限制和基因组进化共同塑造了甲型流感病毒的遗传多样性模式。

IF 5.5 3区医学

Virologica Sinica Pub Date : 2024-08-01 DOI: 10.1016/j.virs.2024.02.005

{"title":"Transmission restriction and genomic evolution co-shape the genetic diversity patterns of influenza A virus","authors":"","doi":"10.1016/j.virs.2024.02.005","DOIUrl":"10.1016/j.virs.2024.02.005","url":null,"abstract":"<div><p>Influenza A virus (IAV) shows an extensive host range and rapid genomic variations, leading to continuous emergence of novel viruses with significant antigenic variations and the potential for cross-species transmission. This causes global pandemics and seasonal flu outbreaks, posing sustained threats worldwide. Thus, studying all IAVs' evolutionary patterns and underlying mechanisms is crucial for effective prevention and control. We developed FluTyping to identify IAV genotypes, to explore overall genetic diversity patterns and their restriction factors. FluTyping groups isolates based on genetic distance and phylogenetic relationships using whole genomes, enabling identification of each isolate's genotype. Three distinct genetic diversity patterns were observed: one genotype domination pattern comprising only H1N1 and H3N2 seasonal influenza subtypes, multi-genotypes co-circulation pattern including majority avian influenza subtypes and swine influenza H1N2, and hybrid-circulation pattern involving H7N9 and three H5 subtypes of influenza viruses. Furthermore, the IAVs in multi-genotypes co-circulation pattern showed region-specific dominant genotypes, implying the restriction of virus transmission is a key factor contributing to distinct genetic diversity patterns, and the genomic evolution underlying different patterns was more influenced by host-specific factors. In summary, a comprehensive picture of the evolutionary patterns of overall IAVs is provided by the FluTyping's identified genotypes, offering important theoretical foundations for future prevention and control of these viruses.</p></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1995820X24000257/pdfft?md5=c9047b76f99283ea406765a10aa07add&pid=1-s2.0-S1995820X24000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997623","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