Virologica SinicaPub Date : 2024-10-01DOI: 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 , Zhou Gong , Miaomiao You , 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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , Jingqi Yang , Xiao Ding , Hangyu Zhou , Na Han , 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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 10.1016/j.virs.2024.08.010
Yuhang Liu , Zhiqiang Liu , Jian Li , Xiaomin Yan , Weidi Xu , Le Yi , Changchun Tu , Biao He
{"title":"Rapid diagnosis of a fox's death case using nanopore sequencing reveals the infection with an Artic-like rabies virus","authors":"Yuhang Liu , Zhiqiang Liu , Jian Li , Xiaomin Yan , Weidi Xu , Le Yi , Changchun Tu , Biao He","doi":"10.1016/j.virs.2024.08.010","DOIUrl":"10.1016/j.virs.2024.08.010","url":null,"abstract":"","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":"142112616","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}
Virologica SinicaPub Date : 2024-10-01DOI: 10.1016/j.virs.2024.09.007
Manman Wu , Yiwei Wang , Chuanjian Wu , Huang Huang , Xinyuan Zhou , Jun Wang , Sidong Xiong , Chunsheng Dong
{"title":"A novel vesicular stomatitis virus armed with IL-2 mimic for oncolytic therapy","authors":"Manman Wu , Yiwei Wang , Chuanjian Wu , Huang Huang , Xinyuan Zhou , Jun Wang , Sidong Xiong , Chunsheng Dong","doi":"10.1016/j.virs.2024.09.007","DOIUrl":"10.1016/j.virs.2024.09.007","url":null,"abstract":"<div><div>Oncolytic virus (OV) is increasingly being recognized as a novel vector in cancer immunotherapy. Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment, so called transformation of ‘cold’ tumors into ‘hot’ tumors. The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators. The Neo-2/15 is a newly de novo synthesized cytokine that functions as both IL-2 and IL-15. However, it specifically lacks the binding site of IL-2 receptor α subunit (CD25), therefore unable to induce the Treg proliferation. In present study, a recombinant vesicular stomatitis virus expressing the Neo-2/15 (VSV<sup>M51R</sup>-Neo-2/15) was generated. Intratumoral delivery of VSV<sup>M51R</sup>-Neo-2/15 efficiently inhibited tumor growth in mice without causing the IL-2-related toxicity previously observed in clinic. Moreover, treatment with VSV<sup>M51R</sup>-Neo-2/15 increased the number of activated CD8<sup>+</sup> T cells but not Treg cells in tumors. More tumor-bearing mice were survival with VSV<sup>M51R</sup>-Neo-2/15 treatment, and the surviving mice displayed enhanced protection against tumor cell rechallenge due to the induced anti-tumor immunity. In addition, combination therapy of OV and anti-PD-L1 immune checkpoint inhibitors further enhanced the anti-tumor immune response. These findings suggest that our novel VSV<sup>M51R</sup>-Neo-2/15 can effectively inhibit the tumor growth and enhance the sensitivity to immune checkpoint inhibitors, providing promising attempts for further clinical trials.</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":"142296609","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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , Yan Liu , Dou Dou , 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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , Xintong Yan , Shaokang Yang , Sichen Ren , Yan Luo , Jiazheng Li , Ping Wang , Yunfeng Shao , Wei Li , Song Li , Jingjing Yang , Ruiyuan Cao , 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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , 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","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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , 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","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":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":"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}
Virologica SinicaPub Date : 2024-10-01DOI: 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 , Xiao-Xu Zhu , Yuanyuan Bie , Bowen Zhang , Wenting Ji , Jing Lou , Muhan Huang , Xi Zhou , 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":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":"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}