{"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":"10.1016/j.virs.2024.09.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 892-908"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virologica SinicaPub Date : 2024-12-01DOI: 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
{"title":"A G3P[3] bat rotavirus can infect cultured human cholangiocytes and cause biliary atresia symptom in suckling mice","authors":"Pengfei Hao , Zhaoxia Pang , Qiaoqiao Qu , Chunmei Cui , Yuhang Jiang , Jing Chen , Zihan Gao , Zhiqiang Xu , Letian Li , Ningyi Jin , Chang Li","doi":"10.1016/j.virs.2024.09.009","DOIUrl":"10.1016/j.virs.2024.09.009","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 974-976"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354980","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 : 2024-12-01DOI: 10.1016/j.virs.2024.10.002
Yan Tong , Wenyi Jin , Xuan Li , Lin Guo , Gang Luo , Qian Meng , Jihong Zhang , Qilian Qin , Huan Zhang
{"title":"Generation and characterization of a novel ovariole cell line derived from Spodoptera frugiperda in China with sensitivity to both SfMNPV and AcMNPV","authors":"Yan Tong , Wenyi Jin , Xuan Li , Lin Guo , Gang Luo , Qian Meng , Jihong Zhang , Qilian Qin , Huan Zhang","doi":"10.1016/j.virs.2024.10.002","DOIUrl":"10.1016/j.virs.2024.10.002","url":null,"abstract":"<div><div><em><em>Spodoptera frugiperda</em></em> multiple nucleopolyhedrovirus (SfMNPV), belonging to the species <em>Alphabaculovirus spofrugiperdae</em>, has been recently registered as an insecticide in China. This virus has a specific effect on the global major agricultural pest <em>Spodoptera frugiperda</em>. To gain insights into viral infection, replication processes, and the complex formation of viral particles, <em>in vitro</em> studies using cell lines are essential tools. Although the IPLB-Sf9 and IPLB-Sf21 cell lines derived from <em>S. frugiperda</em> are widely used for studies on the infection and replication mechanisms of Autographa californica multiple nucleopolyhedrovirus (AcMNPV), their capacity to produce viral polyhedra after SfMNPV infection is not optimal. To address this limitation, a novel cell line named IOZCAS-Sf-1 was developed from a <em>S. frugiperda</em> population in Yunnan, China. The mitochondrial <em>COX1</em> gene analysis confirmed the species origin of the IOZCAS-Sf-1 cell line. Furthermore, a comparative study was carried out to contrast the <em>COX1</em> gene sequence of this novel cell line with that of IPLB-Sf9, highlighting the distinctions between the two. Importantly, the IOZCAS-Sf-1 cells exhibited a remarkable ability to generate polyhedra when infected with AcMNPV and SfMNPV, respectively. Consequently, this cellular lineage is considered a promising and valuable resource. It serves not only to investigate the molecular mechanisms of viral replication and its impact on host cells, but also to explore the transfection efficiency of SfMNPV DNA. This exploration further expands into its potential application in recombinant DNA experiments, laying a theoretical groundwork for the advancement of more effective biopesticides and sustainable agricultural practices.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 929-937"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476075","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 : 2024-12-01DOI: 10.1016/j.virs.2024.10.004
Jiaying Cao , Yuetong Li , Feiyang Xue , Ziyang Sheng , Libo Liu , Yingying Zhang , Lele Wang , Liang Zeng , Yanmin Jiang , Dongying Fan , Fang Li , Jing An
{"title":"Case study: May human norovirus infection be associated with premature delivery?","authors":"Jiaying Cao , Yuetong Li , Feiyang Xue , Ziyang Sheng , Libo Liu , Yingying Zhang , Lele Wang , Liang Zeng , Yanmin Jiang , Dongying Fan , Fang Li , Jing An","doi":"10.1016/j.virs.2024.10.004","DOIUrl":"10.1016/j.virs.2024.10.004","url":null,"abstract":"<div><div>Human norovirus (HuNoV) is the leading cause of acute gastroenteritis. The varying severity of chronic infection in patients with underlying immune deficiencies poses additional burdens on public health. However, the potential effects of HuNoV infection during pregnancy, a specific immune perturbed state, have been rarely reported. Recently, four cases of HuNoV-infected patients in the late stages of pregnancy were admitted to the Guangzhou Women and Children's Medical Center, and premature rupture of membranes as primary adverse outcome was observed in these cases. Samples of fetal accessory tissue were collected from two of these cases at delivery to explore the potential pathogenesis. Pathological analysis showed placental malperfusion in both maternal and fetal vascular, while a decrease in vessels was not observed in villi of placenta. There was obvious pathological change in the chorion of fetal membrane, accompanied by a tendency of Th-1 immune bias. Notably, aggregation of M2 macrophages was observed in the chorion of the fetal membrane, potentially recruited for tissue repair. Next-generation sequencing showed minimal changes in immune pathways within placenta tissue. A gene panel associated with immunosuppression was identified in the fetal membrane of HuNoV-infected women compared to those of normal parturient. Taken together, this study provides clues for the association between the HuNoV and premature delivery, which requires the attention of the clinicians.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 951-962"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569733","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 : 2024-12-01DOI: 10.1016/j.virs.2024.11.005
Feixia Gao , Qi Wang , Chenchen Qiu , Jian Luo , Xiuling Li
{"title":"Pandemic preparedness of effective vaccines for the outbreak of newly H5N1 highly pathogenic avian influenza virus","authors":"Feixia Gao , Qi Wang , Chenchen Qiu , Jian Luo , Xiuling Li","doi":"10.1016/j.virs.2024.11.005","DOIUrl":"10.1016/j.virs.2024.11.005","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 981-985"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772713","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 : 2024-12-01DOI: 10.1016/j.virs.2024.10.003
Siji Chen , Jiang Zhu , Chunting Hua , Chenxi Feng , Xia Wu , Can Zhou , Xianzhen Chen , Boya Zhang , Yaohan Xu , Zeyu Ma , Jianping He , Na Jin , Yinjing Song , Stijn van der Veen , Hao Cheng
{"title":"Single-cell RNA sequencing reveals the diversity of the immunological landscape response to genital herpes","authors":"Siji Chen , Jiang Zhu , Chunting Hua , Chenxi Feng , Xia Wu , Can Zhou , Xianzhen Chen , Boya Zhang , Yaohan Xu , Zeyu Ma , Jianping He , Na Jin , Yinjing Song , Stijn van der Veen , Hao Cheng","doi":"10.1016/j.virs.2024.10.003","DOIUrl":"10.1016/j.virs.2024.10.003","url":null,"abstract":"<div><div>Genital herpes (GH) is a common sexually transmitted disease, which is primarily caused by herpes simplex virus type 2 (HSV-2), and continues to be a global health concern. Although our understanding of the alterations in immune cell populations and immunomodulation in GH patients is still limited, it is evident that systemic intrinsic immunity, innate immunity, and adaptive immunity play crucial roles during HSV-2 infection and GH reactivation. To investigate the mechanisms underlying HSV-2 infection and recurrence, single-cell RNA sequencing (scRNA-seq) was performed on immune cells isolated from the peripheral blood of both healthy individuals and patients with recurrent GH. Furthermore, the systemic immune response in patients with recurrent GH showed activation of classical monocytes, CD4<sup>+</sup> T cells, natural killer cells (NK cells), and plasmacytoid dendritic cells (pDCs), especially of genes associated with the Toll-like receptor signaling pathway and T cell activation. Circulating immune cells in GH patients show higher expression of genes associated with inflammation and antiviral responses both in the scRNA-Seq data set and in independent quantitative real-time polymerase chain reaction (qRT-PCR) analysis and ELISA experiments. This study demonstrated that localized genital herpes, resulting from HSV reactivation, may influence the functionality of circulating immune cells, suggesting a potential avenue for future research into the role of systemic immunity during HSV infection and recurrence.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 860-874"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476076","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 : 2024-12-01DOI: 10.1016/j.virs.2024.10.005
Shihan Chen , Qiqi Zhong , Xuzheng Liao , Haiyang Wang , Bang Xiao , Jianguo He , Chaozheng Li
{"title":"Modulation of the unfolded protein response by white spot syndrome virus via wsv406 targeting BiP to facilitate viral replication","authors":"Shihan Chen , Qiqi Zhong , Xuzheng Liao , Haiyang Wang , Bang Xiao , Jianguo He , Chaozheng Li","doi":"10.1016/j.virs.2024.10.005","DOIUrl":"10.1016/j.virs.2024.10.005","url":null,"abstract":"<div><div>Outbreaks of diseases are often linked to environmental stress, which can lead to endoplasmic reticulum (ER) stress and subsequently trigger the unfolded protein response (UPR). The replication of the white spot syndrome virus (WSSV), the most serious pathogen in shrimp aquaculture, has been shown to rely on the UPR signaling pathway, although the detailed mechanisms remain poorly understood. In this study, we discovered that WSSV enhances its replication by hijacking the UPR pathway via the viral protein wsv406. Our analysis revealed a significant upregulation of wsv406 in the hemocytes and gills of infected shrimp. Mass spectrometry analysis identified that wsv406 interacts specifically with the immunoglobulin heavy-chain-binding protein (BiP) in shrimp <em>Litopenaeus vannamei</em>. Further examination revealed that wsv406 binds to multiple domains of LvBiP, inhibiting its ATPase activity without disrupting its binding to UPR stress receptors. Silencing either wsv406 or LvBiP resulted in a reduction in WSSV replication and improved shrimp survival rates. Further, wsv406 activation of the PRKR-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α) and activating transcription factor 6 (ATF6) pathways was demonstrated by a decrease in the phosphorylation of eIF2α and the nuclear translocation of ATF6 when wsv406 was silenced during WSSV infection. This activation facilitated the transcription of <em>WSSV</em> genes, promoting viral replication. In summary, these findings reveal that wsv406 manipulates the host UPR by targeting LvBiP, thereby enhancing WSSV replication through the PERK-eIF2α and ATF6 pathways. These insights into the interaction between WSSV and host cellular machinery offer potential targets for developing therapeutic interventions to control WSSV outbreaks in shrimp aquaculture.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 938-950"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569735","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.2024.08.011
Jiali Si, Xi Wang, Manli Wang, Zhihong Hu
{"title":"The 2024 National Symposium on Insect Virology held in Qingdao","authors":"Jiali Si, Xi Wang, Manli Wang, Zhihong Hu","doi":"10.1016/j.virs.2024.08.011","DOIUrl":"10.1016/j.virs.2024.08.011","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 843-844"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112617","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.2024.08.002
Xiangkuan Zheng , Meihan Liu , Pei Li , Sixiang Xu , Long Chen , Guoxin Xu , Xiaoxiao Pang , Hong Du , Yishan zheng , Xiang Huo , Zhongming Tan , Juan Li , Zhirong Li , Wei Zhang
{"title":"Antibacterial activity evaluation of a novel K3-specific phage against Acinetobacter baumannii and evidence for receptor-binding domain transfer across morphologies","authors":"Xiangkuan Zheng , Meihan Liu , Pei Li , Sixiang Xu , Long Chen , Guoxin Xu , Xiaoxiao Pang , Hong Du , Yishan zheng , Xiang Huo , Zhongming Tan , Juan Li , Zhirong Li , Wei Zhang","doi":"10.1016/j.virs.2024.08.002","DOIUrl":"10.1016/j.virs.2024.08.002","url":null,"abstract":"<div><div><em>Acinetobacter baumannii</em> (<em>A. baumannii</em>) poses a serious public health challenge due to its notorious antimicrobial resistance, particularly carbapenem-resistant <em>A. baumannii</em> (CRAB). In this study, we isolated a virulent phage, named P1068, from medical wastewater capable of lysing CRAB, primarily targeting the K3 capsule type. Basic characterization showed that P1068 infected the <em>A. baumannii</em> ZWAb014 with an optimal MOI of 1, experienced a latent period of 10 min and maintained stability over a temperature range of 4–37 °C and pH range of 3–10. Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus <em>Obolenskvirus</em> of the <em>Caudoviricetes</em> class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses (ICTV). Additionally, according to classical morphological classification, P1068 is identified as a T4-like phage (<em>Myoviridae</em>). Interestingly, we found that the tail fiber protein (TFP) of P1068 shares 74% coverage and 88.99% identity with the TFP of a T7-like phage (<em>Podoviridae</em>), AbKT21phiIII (<span><span>NC_048142.1</span><svg><path></path></svg></span>). This finding suggests that the <em>TFP</em> gene of phages may undergo horizontal transfer across different genera and morphologies. <em>In vitro</em> antimicrobial assays showed that P1068 exhibited antimicrobial activity against <em>A. baumannii</em> in both biofilm and planktonic states. In mouse models of intraperitoneal infection, P1068 phage protected mice from <em>A. baumannii</em> infection and significantly reduced bacterial loads in various tissues such as the brain, blood, lung, spleen, and liver compared to controls. In conclusion, this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilm-forming <em>A. baumannii</em> infections, and expands the understanding of horizontal transfer of phage <em>TFP</em> genes.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 5","pages":"Pages 767-781"},"PeriodicalIF":5.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890203","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}