{"title":"Elevated interferon-induced transmembrane protein 3 in platelets and megakaryocytes suppresses Crimean-Congo hemorrhagic fever viral infection by interacting with glycoprotein Gc.","authors":"Jingyuan Zhang, Yaohui Fang, Chenhui Lin, Xiaoli Wu, Chaoxiong Yue, Fei Deng, Shu Shen","doi":"10.1016/j.virs.2025.05.002","DOIUrl":"10.1016/j.virs.2025.05.002","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a hemorrhagic fever caused by infection with the CCHF virus (CCHFV) and has a mortality rate of up to 30 %. Thrombocytopenia is a hallmark of CCHF; however, the mechanisms underlying this manifestation remain poorly understood. In addition to hemostasis, platelets play a crucial role in recognizing pathogens and mediating immune responses. We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice. Interferon-induced transmembrane protein 3 (IFITM3), a known antiviral factor, was significantly upregulated. The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01, considered a parental cell line of platelets. Although the CCHFV infection rate was limited, MEG-01 cells maintained the infection and replication of CCHFV, leading to increased IFITM3 protein expression. We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection, whereas IFITM3 knockout promoted viral infection. An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified, which suppressed CCHFV entry into cells. The IFITM3 CIL-TMD domain is critical for this interaction. These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection. Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses, including CCHFV, which may reduce platelet consumption and destruction caused by CCHFV infection. These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132654","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":"Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus.","authors":"Hao-Feng Lin, Ren-Di Jiang, Rui-Xin Qin, Bing Yao, Wen-Tao Zeng, Yun Gao, Ai-Min Shi, Jian-Min Li, Mei-Qin Liu","doi":"10.1016/j.virs.2025.05.001","DOIUrl":"10.1016/j.virs.2025.05.001","url":null,"abstract":"<p><p>Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102769","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 : 2025-04-12DOI: 10.1016/j.virs.2025.04.005
Yang Xu, Qiushi Zhang, Guoli Hou, Liang Hu, Tiaoyi Xiao, Xinyu Liang, Deliang Li, Junhua Li
{"title":"Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.","authors":"Yang Xu, Qiushi Zhang, Guoli Hou, Liang Hu, Tiaoyi Xiao, Xinyu Liang, Deliang Li, Junhua Li","doi":"10.1016/j.virs.2025.04.005","DOIUrl":"10.1016/j.virs.2025.04.005","url":null,"abstract":"<p><p>Deamidation, a type of post-translational modification commonly considered a hallmark of protein \"aging\" and function decay, is increasingly recognized for its pivotal role in regulating biological processes and viral infection. Our previous study has demonstrated that the deamidation of replication and transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS), hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTA deamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFAS-mediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factor-kappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activation of viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process of several viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploited to enhance viral infection via deamidation regulation.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987468","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 : 2025-04-12DOI: 10.1016/j.virs.2025.04.004
Yan Ran, Zinuo Chen, Carolina Q Sacramento, Lingyuan Fan, Qinghua Cui, Lijun Rong, Ruikun Du
{"title":"Scutellaria barbata D. Don extracts alleviate SARS-CoV-2 induced acute lung injury by inhibiting virus replication and bi-directional immune modulation.","authors":"Yan Ran, Zinuo Chen, Carolina Q Sacramento, Lingyuan Fan, Qinghua Cui, Lijun Rong, Ruikun Du","doi":"10.1016/j.virs.2025.04.004","DOIUrl":"10.1016/j.virs.2025.04.004","url":null,"abstract":"<p><p>The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents. In the present study, we examined the therapeutic effect of the Chinese medicinal herb, Scutellaria barbata D. Don (SBD), against SARS-CoV-2 infection both in vitro and in vivo. Using a viral replicon particle (VRP)-based mouse model of SARS-CoV-2 infection, our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia. In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication. Mechanistic studies demonstrated that SBD can act against SARS-CoV-2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases, via a combination of multiple active constituents. Moreover, SBD can modulate the host inflammation response in a bi-directional manner, which also contribute to the mitigation of viral induced acute lung injury. In summary, our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056142","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":"Differential susceptibility of immunodeficient mice to MPXV infection and the impact of various inoculation routes.","authors":"Xiaohan Wang, Shaowen Shi, Xiaoxuan Nie, Yongyang Sun, Jinglei Hu, Manlin He, Wenhao Ren, Yuxing Wang, Zhendong Guo, Gonghe Li, Changbo Ou, Xiao Li, Zongzheng Zhao","doi":"10.1016/j.virs.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.001","url":null,"abstract":"<p><p>Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, caused a large-scale global outbreak in 2022. Developing mouse models for MPXV infection is crucial for advancing research on vaccines and therapeutic interventions. To address this, we conducted a comparative study on the susceptibility of six mouse strains-severe combined immune-deficiency (SCID), nude, genetically diabetic (db/db) and obese (ob/ob), C57BL/6J, and BALB/c-to MPXV infection. Mouse strains were infected with MPXV via intranasal inoculation, and body weight changes and mortality were monitored post-infection. Additionally, the tissue distribution of MPXV and the pathological changes in the lung tissues of the infected mice were evaluated. The results demonstrated that SCID and nude mice exhibited significant weight loss following MPXV infection, with 100 % mortality observed in SCID mice, while no mortality occurred in nude mice. In contrast, the other mouse strains showed no significant weight loss or mortality. Notably, the viral load in the lung tissues of SCID and nude mice was the highest among the tested strains. Furthermore, we investigated the impact of different inoculation routes-intranasal (I.N.), intraperitoneal (I.P.), and intravenous (I.V.)-on the pathogenicity of MPXV in mice. The results revealed that the intravenous route induced more pronounced pathogenic effects compared to the intranasal and intraperitoneal routes. In summary, this study provides valuable insights into the development of MPXV-infected mouse models, offering a foundation for further research on MPXV pathogenesis and therapeutic drug development.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050603","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 : 2025-04-07DOI: 10.1016/j.virs.2025.04.002
Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou
{"title":"WITHDRAWN: Comparative metatranscriptome analysis in gut reveals insignificant host or microbiota changes in SARS-related coronavirus naturally infected bats.","authors":"Qi Wang, Shi-Qiang Mei, Tian-Yi Dong, Jia Su, Yuan-Fei Pan, Yan Zhu, Ke Wu, Li-Biao Zhang, Mang Shi, Peng Zhou","doi":"10.1016/j.virs.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.virs.2025.04.002","url":null,"abstract":"<p><p>The publisher regrets that this article has withdrawn.\u0000The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026119","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}