Virologica SinicaPub Date : 2026-04-02DOI: 10.1016/j.virs.2026.03.017
Yuelin Wang, Wei Dou, Yingying Chen, Ke Liu, Mengjun Li, Tyuji Hoshino, Yushan Jiang, Vladislav Victorovich Khrustalev, Alexey V Churov, Alexander N Orekhov, Wei Zhao, Ling Li, Yang Yang, Chenguang Shen
{"title":"Development and characterization of neutralizing monoclonal antibodies against clinically relevant human adenovirus subgroup B serotypes.","authors":"Yuelin Wang, Wei Dou, Yingying Chen, Ke Liu, Mengjun Li, Tyuji Hoshino, Yushan Jiang, Vladislav Victorovich Khrustalev, Alexey V Churov, Alexander N Orekhov, Wei Zhao, Ling Li, Yang Yang, Chenguang Shen","doi":"10.1016/j.virs.2026.03.017","DOIUrl":"10.1016/j.virs.2026.03.017","url":null,"abstract":"<p><p>Human adenoviruses (HAdVs), particularly subgroup B serotypes HAdV-3 and HAdV-55, are associated with severe respiratory disease and currently lack targeted therapies. While neutralizing monoclonal antibodies (nMAbs) offer promising therapeutic potential, the specific nMAbs targeting these serotypes remain poorly characterized. Therefore, this study aimed to generate and evaluate the efficacy of serotype-specific nMAbs against HAdV-3 and HAdV-55. Mice were immunized with HAdV-3 virions, HAdV-55 virions, or recombinant fiber knob proteins (HAdV-55/-7) for the generation of serotype-specific nMAbs, and their efficacy was systematically evaluated using in vitro assays and an in vivo tree shrew model. Through comprehensive screening, eleven MAbs were identified with specificity against HAdV-3 (six clones) or HAdV-55/-7 fiber knob (five clones). Four nMAbs exhibited potent neutralizing activity: 13F12 (half-maximal inhibitory concentration, IC<sub>50</sub>: 3.8 μg/mL), 8D2 (IC<sub>50</sub>: 15.1 μg/mL), 3A3 (IC<sub>50</sub>: 14.9 μg/mL) against HAdV-3 virions, and 8F2 with neutralizing efficacy against HAdV-55 virions (IC<sub>50</sub>: 30.4 μg/mL). Western blot analysis revealed that MAbs 13F12 and 8F2 targeted the fiber protein, whereas 8D2 and 3A3 bound to the hexon protein. Furthermore, in vivo evaluations demonstrated that 13F12 significantly reduced viral loads in nasal turbinates and attenuated lung pathology in HAdV-3-infected tree shrews. Mechanistically, all tested anti-HAdV-3 nMAbs inhibited infection by blocking viral attachment (P < 0.01 vs. controls). In conclusion, this study underscores the therapeutic potential of targeting viral entry and highlights 13F12 as a promising candidate for HAdV prophylaxis.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619130","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}
Virologica SinicaPub Date : 2026-04-01DOI: 10.1016/j.virs.2026.03.016
Qiongzhen Zeng, Weixiangmin Zou, Jiaqi Wu, Menghe Li, Zexu Wang, Caiwenjie La, Cuifang Ye, Zhe Ren, Yifei Wang, Kai Zheng
{"title":"Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation.","authors":"Qiongzhen Zeng, Weixiangmin Zou, Jiaqi Wu, Menghe Li, Zexu Wang, Caiwenjie La, Cuifang Ye, Zhe Ren, Yifei Wang, Kai Zheng","doi":"10.1016/j.virs.2026.03.016","DOIUrl":"10.1016/j.virs.2026.03.016","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) infection can induce herpes simplex encephalitis (HSE), a life-threatening neurological disorder characterized by active viral replication within the central nervous system accompanied by excessive neuroinflammatory responses. Cepharanthine hydrochloride (CH) is a natural bisbenzylisoquinoline alkaloid with diverse pharmacological activities. CH was evaluated for its antiviral and anti-inflammatory activities against HSV-1 infection. In microglia, CH markedly inhibited viral replication and suppressed STING-NF-κB signaling, thereby reducing HSV-1-associated neuroinflammation. During HSV-1 infection, CH binds to Nrf2, disrupting Keap1-Nrf2 interaction and subsequent ubiquitination. This hindered Nrf2 degradation and attenuated STING activation. In an HSE mouse model, CH significantly reduced viral loads in brain tissue, improved survival rates, prevented weight loss, and alleviated neurological symptoms. Furthermore, CH promoted the accumulation of Nrf2 and inhibited the STING-NF-κB signaling pathway in vivo. Collectively, these results indicate that CH represents a potential antiviral strategy for HSE.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616882","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}
{"title":"Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.","authors":"Lixia Hui, Danyu Qian, Yulei Guo, Zhengjun Yi, Tao Guo, Aixin Li, Ying Wu","doi":"10.1016/j.virs.2026.03.014","DOIUrl":"10.1016/j.virs.2026.03.014","url":null,"abstract":"<p><p>Blood-tissue barriers are specialized interfaces that safeguard organ homeostasis by restricting pathogen dissemination. Zika virus (ZIKV), an emerging flavivirus of global concern, exhibits an exceptional ability to breach multiple barriers-including the blood-brain, blood-placental, blood-testis, and blood-retinal barriers-enabling neuroinvasion, vertical and sexual transmission, and ocular disease. ZIKV employs diverse strategies to cross these barriers: receptor-mediated entry, disruption of tight junctions, and hijacking immune cells or extracellular vesicles as viral carriers. Adaptive mutations further refine tissue tropism and enhance barrier traversal efficiency. Insights from cell culture, organoid, animal, and ex vivo tissue models reveal not only the conserved and tissue-specific mechanisms of barrier penetration but also the downstream pathological consequences in the affected organs. Understanding how ZIKV breaches these interfaces and induces organ-specific pathology deepens our knowledge of host-pathogen interactions and provides a framework for designing barrier-protective and disease-mitigating strategies against ZIKV and other pathogens that breach blood-tissue barriers.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582471","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}
Virologica SinicaPub Date : 2026-03-27DOI: 10.1016/j.virs.2026.03.011
Lei Deng, Jia-Ye Liu, Ya-Xuan Peng
{"title":"Structural vaccinology expedites rational design of next-generation vaccines for influenza and respiratory syncytial virus.","authors":"Lei Deng, Jia-Ye Liu, Ya-Xuan Peng","doi":"10.1016/j.virs.2026.03.011","DOIUrl":"10.1016/j.virs.2026.03.011","url":null,"abstract":"<p><p>Vaccination stands as the single most effective and cost-efficient public health intervention in human history, serving as a cornerstone of modern medicine that profoundly transforms global health outcomes. Beyond preventing disease, it acts as a catalyst for equitable socioeconomic development. In recent decades, recurrent seasonal viral outbreaks and sporadic yet catastrophic pandemics have continued to pose challenges to global public health systems. Traditional vaccine technologies, however, not only often fall short in protection efficacy, but also fail to keep pace with the evolving demands of next-generation vaccine development. These scientific gaps have directed cutting-edge research to prioritize critical objectives in terms of enhancing antigen effectiveness, achieving stable pan-protection against diverse variant strains, and strengthening production robustness. The advent of genomics spurred the emergence of reverse vaccinology 1.0, leading to breakthroughs like the MenB vaccine. Today, the advanced reverse vaccinology 2.0 paradigm thoroughly redefines vaccine design process by organically integrating human immunology with state-of-the-art computational protein structure analysis tools. This review explores the transformative shifts in influenza and respiratory syncytial virus vaccine development, along with specific case studies, to deepen understanding of the evolving principles and methodologies in novel vaccine designs and offer strategic insights for addressing emerging infectious pathogens.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575342","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}
Virologica SinicaPub Date : 2026-03-27DOI: 10.1016/j.virs.2026.03.012
Li Yang, Shuyu Xin, Shen Li, Pengfei Cao, Zeyu Sun, Mingjuan Jiang, Yujie Xin, Xiaoling Su, Jing Yang, Jianhong Lu
{"title":"EBV nuclear antigen 1 hijacks DDX5/BZLF1 axis to facilitate viral lytic replication.","authors":"Li Yang, Shuyu Xin, Shen Li, Pengfei Cao, Zeyu Sun, Mingjuan Jiang, Yujie Xin, Xiaoling Su, Jing Yang, Jianhong Lu","doi":"10.1016/j.virs.2026.03.012","DOIUrl":"10.1016/j.virs.2026.03.012","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) lytic replication is a key driver of viral dissemination and tumorigenicity in epithelial malignancies, such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). However, the underlying molecular mechanism and effective therapeutic strategy remain largely unknown. Here, we analyzed the EBV nuclear antigen 1 (EBNA1) interactome and identified DEAD-box helicase 5 (DDX5) as its novel partner. The N-terminal region (amino acids 1-88) of EBNA1 and the C-terminal domain of DDX5 were crucial for their binding. EBNA1 stabilized the DDX5 protein by impeding its proteasomal degradation via K48-linked polyubiquitin. EBNA1 facilitated EBV lytic replication in a DDX5-dependent manner. Furthermore, DDX5 bound to the promoter of BZLF1, which is the key switch of EBV reactivation, thus transactivating BZLF1 to drive viral lytic replication. Moreover, the small molecule inhibitor FL118 was able to disrupt this process by promoting DDX5 degradation, unveiling FL118 as a new potential antiviral drug. Our findings established a new functional axis of EBNA1/DDX5/BZLF1, adding to the knowledge about the role of EBNA1 in the regulation of EBV life cycle, particularly lytic replication. The study also provided a potential therapeutic strategy for EBV-associated epithelial tumors.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575311","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}
{"title":"Tupaia belangeri better reflects the typical symptoms of Chikungunya virus infection than mice: A comparative study.","authors":"Yan Guo, Mengyuan Zheng, Qi Wang, Hui Xiao, Li Liu, Shuwei Dong, Yonghan Luo, Zhouling Pan, Yujie Xiang, Yanxian Jiang, Xiao Chen, Hailin Tang, Yuemei Feng, Yue Feng, Xueshan Xia","doi":"10.1016/j.virs.2026.03.013","DOIUrl":"10.1016/j.virs.2026.03.013","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) infection in humans is typically characterized by acute febrile illness, rash, and polyarthralgia, and often progresses to chronic arthralgia. However, existing small-animal models fail to capture both the acute and chronic phases of the disease. In this study, we compared Chinese tree shrews (Tupaia belangeri) and C57BL/6 mice in terms of infection dynamics, viral characteristics, histopathological changes, and immune responses. Following dual-site inoculation (subcutaneous injection into the abdomen and footpad), Tupaia belangeri exhibited typical symptoms that more closely resembled those of humans, including pronounced fever, foot swelling, and skin lesions, and were accompanied by higher and more sustained viral loads in blood and multiple tissues. Histopathological examination revealed marked inflammation and tissue damage in muscle and joint tissues, consistent with pathological changes observed in humans. Transcriptomic analysis further demonstrated significant upregulation of multiple key immune-related genes (CXCL10, ISG15, IFIT3, SERPING1, MCEMP1, IFI6), indicating a human-like immune response profile. Collectively, our results show that Tupaia belangeri faithfully mirrors the infection features, viral dynamics, and immune responses of human CHIKV infection, establishing it as a valuable model for dissecting disease mechanisms and testing vaccines or antiviral therapies.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575412","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}
Virologica SinicaPub Date : 2026-03-24DOI: 10.1016/j.virs.2026.03.009
Yutong Wei, Qiyan Liu, Zhen Gong, Guan-Zhu Han
{"title":"Unveiling the cryptic diversity and distribution of elements related to virophage mavirus through deep mining of pPolB proteins.","authors":"Yutong Wei, Qiyan Liu, Zhen Gong, Guan-Zhu Han","doi":"10.1016/j.virs.2026.03.009","DOIUrl":"10.1016/j.virs.2026.03.009","url":null,"abstract":"<p><p>Virophages are unique double-stranded DNA (dsDNA) viruses that parasitize viruses of Nucleocytoviricota (NCVs). While conventionally viewed as a viral group, growing evidence suggests that \"virophage\" is better understood as a parasitic lifestyle, rather than a natural group. Despite this conceptual shift, their diversity and evolution remain largely obscure and contentious. Through deep mining of protein-primed type B DNA polymerase (pPolB) in 7041 eukaryotic genomes and 12,053 metagenomes sampled globally, we expand the diversity of pPolB-carrying mavirus virophage-related elements (pMVREs), which include virophages, transpovirons, and Polinton-like viruses (PLVs). Our phylogenomic and metagenomic mining reveals the widespread distribution of pMVREs in eukaryotic genomes (97/7041, 1.38%) and global environments (2450/12053, 20.33%). pMVREs possess genome architectures of high plasticity and promiscuity. The presence of pMVREs and NCVs is statistically correlated in both eukaryotic genomes and global metagenomes, supporting a specific co-occurrence association between pMVREs and NCVs. Moreover, pMVRE diversity and composition exhibit strong heterogeneity across global ecosystems. Together, this study unveils a vast diversity of virophage-related elements and provides insights into the intricate relationship among virophages, transpovirons, PLVs, pMVREs, and NCVs.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522292","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}
Virologica SinicaPub Date : 2026-03-20DOI: 10.1016/j.virs.2026.03.008
Min Chen, Huichao Chen, Yanling Ma, Manhong Jia, Wenfei Ding
{"title":"Identification of a novel HIV-1 circulating recombinant form (CRF161_0107) from CRF01_AE-C5 lineage among men who have sex with men in southwestern China.","authors":"Min Chen, Huichao Chen, Yanling Ma, Manhong Jia, Wenfei Ding","doi":"10.1016/j.virs.2026.03.008","DOIUrl":"10.1016/j.virs.2026.03.008","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499852","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}