{"title":"The Single Amino Acid Change of R516K Enables Efficient Generation of Vesicular Stomatitis Virus-Based Crimean–Congo Hemorrhagic Fever Reporter Virus","authors":"Xue Ma, Yanlong Ma, Ziqiao Wang, Fei Feng, Yutong Han, Xinran Sun, Liushuai Li, Zhichao Gao, Manli Wang, Rong Zhang","doi":"10.1002/jmv.70457","DOIUrl":"https://doi.org/10.1002/jmv.70457","url":null,"abstract":"<div>\u0000 \u0000 <p>Crimean–Congo hemorrhagic fever virus (CCHFV) is a medically important tick-borne virus, causing severe hemorrhagic diseases in humans. There are no approved vaccines and therapeutics for CCHFV infection. The study of CCHFV authentic virus requires biosafety level 3 facilities, hindering the research and development of antivirals. Here we report the generation of a recombinant vesicular stomatitis virus (VSV) bearing both CCHFV glycoprotein precursor (GPC) and EGFP reporter (rVSV-CCHFV-GFP). We also find that the acquisition of an unexpected single R516K mutation in the GPC protein enables the packaging of high-titer pseudotyped particles. The replication-competent rVSV-CCHFV-GFP reporter virus resembles the entry properties of the authentic virus and allows for rapid assessment of susceptible cell lines, neutralizing antibodies, and host entry factors such as heparan sulfate in fluorescence-based assays. This study provides a valuable strategy for packaging of high-titer CCHFV pseudovirus, and the tool generated here can be served for the identification and evaluation of countermeasures against the cell entry of CCHFV.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323650","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":"Comparison of Clinical Features and Severity of Subgroup A and B Respiratory Syncytial Virus Infection","authors":"Ya-Li Hu, Shu-Yuan Ho, Ai-Ling Cheng, Yu-Tsung Huang, Chi-Tai Fang, Luan-Yin Chang","doi":"10.1002/jmv.70453","DOIUrl":"https://doi.org/10.1002/jmv.70453","url":null,"abstract":"<div>\u0000 \u0000 <p>Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract disease. This study investigated the clinical differences between RSV subgroups A and B using data from a university-affiliated medical center in Taiwan from September 2018 to August 2023. RSV was confirmed via viral culture or rapid antigen tests, with peak circulation occurring from August to January. Among 152 RSV isolates, subgroup A (61.2%) was more common than subgroup B. Children aged ≥ 6 months had more frequent fever (94% vs. 67%), longer febrile duration (3 vs. 1 days), and more comorbidities (45% vs. 14%) than those < 6 months (all <i>p</i> < 0.001). Immunocompromised patients, primarily adults, had higher intubation rates and significantly greater mortality (27%), which occurred exclusively in this group. Compared to subgroup B, subgroup A was associated with higher fever incidence (91% vs. 75%, <i>p</i> = 0.005), longer fever (2 vs. 1 day, <i>p</i> = 0.03), higher CRP (1.2 vs. 0.3 mg/dL, <i>p</i> = 0.001), and more bacterial coinfection/co-detection (29% vs. 10%, <i>p</i> = 0.006). Five G protein substitutions, notably S283P, emerged after December 2022. New clades A.D.3.5, A.D.5, A.D.5.2, and B.D.E.1 were identified post-COVID, with B.D.E.1 linked to increased dyspnea. Ongoing surveillance is warranted to monitor emerging variants and guide preventive strategies in high-risk groups.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323651","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":"Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application","authors":"Ling Yin, Hongliang He, Hongliang Zhang, Yuhua Shang, Chengbo Fu, Songquan Wu, Tengchuan Jin","doi":"10.1002/jmv.70447","DOIUrl":"https://doi.org/10.1002/jmv.70447","url":null,"abstract":"<p>Adeno-associated virus (AAV) is a non-enveloped DNA virus infecting a wide variety of species, tissues, and cell types, which is recognized as a safe and effective method for delivering therapeutic transgenes. AAV vector is the most popular viral gene delivery system in clinical delivery systems with unique and multiple advantages, such as tissue tropism, transduction specificity, long-lasting gene expression, low immune responses, and without host chromosome incorporation. Till now, four AAV-based gene therapy drugs have already been approved by the US Food and Drug Administration (FDA) or European Medicines Agency (EMA). Despite the success of AAV vectors, there are still some remaining challenges that limit further usage, such as poor packaging capacity, low organ specificity, pre-existing humoral immunity, and vector dose-dependent toxicity. In the present review, we address the different approaches to optimize AAV vector delivery system with a focus on capsid engineering, packaging capacity, and immune response at the clinical level. The review further investigates the potential of manipulating AAV vectors in preclinical applications and clinical translation, which emphasizes the challenges and prospects in viral vector selection, drug delivery strategies, immune reactions in cancer, neurodegenerative disease, retinal disease, SARS-CoV-2, and monkeypox. Finally, it forecasts future directions and potential challenges of artificial intelligence (AI), vaccines, and nanobodies, which emphasizes the need for ethical and secure approaches in AAV application.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315305","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}
XiaoYue Tang, YaNan Zhou, Yan Sun, Tao Ding, QiaoChu Wang, Chunmei Shi, Zhiyi Zhang, YeHong Yang, Yue Wu, JiangFeng Liu, ShuaiYao Lu, JunTao Yang
{"title":"Proteomics and Phosphoproteomics Characteristics of the Rhesus Macaque Lung Infected With Original SARS-CoV-2, Delta, and Omicron Variants","authors":"XiaoYue Tang, YaNan Zhou, Yan Sun, Tao Ding, QiaoChu Wang, Chunmei Shi, Zhiyi Zhang, YeHong Yang, Yue Wu, JiangFeng Liu, ShuaiYao Lu, JunTao Yang","doi":"10.1002/jmv.70446","DOIUrl":"https://doi.org/10.1002/jmv.70446","url":null,"abstract":"<div>\u0000 \u0000 <p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains mutate rapidly, making it crucial to study their molecular mechanisms for swift vaccine and drug development. Here, we utilized host lung proteomic and phosphoproteomic profiling to investigate the underlying pathology caused by the variants. Lung tissues infected with wild-type GD108, Delta, or Omicron BA.1 variants showed overexpression of proteins and phosphoproteins linked to the innate immune pathway, particularly in the Omicron group, with high activation of NOD-receptor and RIG-I like receptor signaling pathways. Protein-protein interaction (PPI) analysis revealed six key proteins, including antiviral innate immune response receptor RIG-I (DDX58), and five interferon-related proteins (IFIT2, ISG15, MX1, STAT1, and EIF2AK2), highlighting the importance of the innate immune response in combating all three variants. Kinase prediction analysis suggested that six kinases (DAPK1, DAPK2, DAPK3, PRACK, TTK, and MAP2K2), potentially inhibited by Fostamatinib, were activated across all three variants, and might be potential drug targets, pending further verification. Omicron infection, compared to other mutants, significantly disrupted proteins related to pulmonary structural support, like integrin and collagens, and inhibited efferocytosis, reducing the host's ability to eliminate the pathogen. These findings suggest that innate immune activation and structural disruption may contribute to Omicron-related pathology, potentially being useful for research into the molecular mechanisms underlying lung injury from SARS-CoV-2 variants.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315304","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}
Ketty Gleyzer de Oliveira, Mariana Pinheiro Alves Vasconcelos, Julia Teixeira Ton, Silvia Naomi de Oliveira Uehara, Roberta Sitnik, Denize Ornelas Pereira Salvador de Oliveira, Layze Castberg, Ricardo Andreotti Siqueira, Peter James Robinson, Thaís Senna de Paula Domingues, Caroline Thomas Panico, César Augusto Inoue, Maira Marranghello Maluf, Fernanda de Mello Malta, Deyvid Amgarten, Erick Dorlass, Pedro Sebe, Arlene S. Pinto, Cirley M. D. O. Lobato, Adalgisa Ferreira, Elodie Hyppolito, Raymundo Paraná, Maria Isabel Schinoni, Edmundo Pessoa de Almeida Lopes, Magali C. Luiz, Raquel F. L. Garcia, Dennis Armando Bertolini, Mário Reis Álvares-da-Silva, Raul Salinas Arrojo, Eduardo Emerim, Gabriela P. Coral, Paulo R. Acosta, Marcello Lucena, Rosângela Teixeira, Mônica da Costa Guedes, Livia Melo Villar, Lia Lewis Ximenez, Clarice Gdalevici, Maria Cássia Jacintho Mendes-Correa, Flair José Carrilho, Gerson Sobrinho Salvador de Oliveira, Paulo Roberto A. Ferreira, Maria Lucia Gomes Ferraz, Ana Catharina de Seixas Santos Nastri, Pablo Andres Munoz Torres, Glória Selegatto, Luciana Vilas Boas Casadio, Simone Tenore, Olavo Henrique Munhoz Leite, Fernanda Fernandes Souza, Tania Reuter, Francisco Souto, Michele Nascimento-Sales, Ana Paula Maciel Gurski, Andréa Salomão, Bruna Emanuelle Alvarenga Fanis, Maria Cristina Pimenta, Elton Carlos de Almeida, Flávia Moreno Alves de Souza, Gerson Fernando Mendes Pereira, Mario Peribañez Gonzalez, Michele Soares Gomes-Gouvea, Raymundo Soares de Azevedo, João Renato Rebello Pinho
{"title":"A Comprehensive Molecular and Serological Investigation of Hepatitis A Virus Among Patients With Suspected Acute Hepatitis: A Brazilian Study","authors":"Ketty Gleyzer de Oliveira, Mariana Pinheiro Alves Vasconcelos, Julia Teixeira Ton, Silvia Naomi de Oliveira Uehara, Roberta Sitnik, Denize Ornelas Pereira Salvador de Oliveira, Layze Castberg, Ricardo Andreotti Siqueira, Peter James Robinson, Thaís Senna de Paula Domingues, Caroline Thomas Panico, César Augusto Inoue, Maira Marranghello Maluf, Fernanda de Mello Malta, Deyvid Amgarten, Erick Dorlass, Pedro Sebe, Arlene S. Pinto, Cirley M. D. O. Lobato, Adalgisa Ferreira, Elodie Hyppolito, Raymundo Paraná, Maria Isabel Schinoni, Edmundo Pessoa de Almeida Lopes, Magali C. Luiz, Raquel F. L. Garcia, Dennis Armando Bertolini, Mário Reis Álvares-da-Silva, Raul Salinas Arrojo, Eduardo Emerim, Gabriela P. Coral, Paulo R. Acosta, Marcello Lucena, Rosângela Teixeira, Mônica da Costa Guedes, Livia Melo Villar, Lia Lewis Ximenez, Clarice Gdalevici, Maria Cássia Jacintho Mendes-Correa, Flair José Carrilho, Gerson Sobrinho Salvador de Oliveira, Paulo Roberto A. Ferreira, Maria Lucia Gomes Ferraz, Ana Catharina de Seixas Santos Nastri, Pablo Andres Munoz Torres, Glória Selegatto, Luciana Vilas Boas Casadio, Simone Tenore, Olavo Henrique Munhoz Leite, Fernanda Fernandes Souza, Tania Reuter, Francisco Souto, Michele Nascimento-Sales, Ana Paula Maciel Gurski, Andréa Salomão, Bruna Emanuelle Alvarenga Fanis, Maria Cristina Pimenta, Elton Carlos de Almeida, Flávia Moreno Alves de Souza, Gerson Fernando Mendes Pereira, Mario Peribañez Gonzalez, Michele Soares Gomes-Gouvea, Raymundo Soares de Azevedo, João Renato Rebello Pinho","doi":"10.1002/jmv.70449","DOIUrl":"https://doi.org/10.1002/jmv.70449","url":null,"abstract":"<p>Hepatitis A Virus (HAV) infects millions of individuals annually and is a major cause of acute viral hepatitis worldwide. This study aims to (1) assess HAV infection in suspected acute hepatitis patients at public healthcare institutions in Brazil; (2) evaluate the proportion of immunized individuals against HAV; (3) identify HAV genotypes; (4) examine the association between HAV infection and demographic data, as well as exposure to risk factors. This is a prospective, observational multicenter study conducted in primary health services in Brazil from October 2019 to May 2023, involving 1721 patients with suspected acute hepatitis. Acute HAV infection was identified in 108 (6.3%) patients, predominantly in young men (80%) and from South and Southeast regions of Brazil (97%). Anti-HAV IgG, indicating previous exposure or vaccination, was detected in 78.6% of individuals (74% in the South to 91% in the North). Genotype I.A was found in all cases and approximately 450 mutations were identified, most of them in the structural proteins VP1-3. Two viral groups were identified and related to two introductions of the virus: cosmopolitan sequences from North America, South America, and Europe, and a minor group of Brazilian sequences similar to Asian and South American ones. The high incidence of acute HAV infections highlights the need for targeted prevention and vaccination strategies. The characterization of HAV genetic diversity and molecular epidemiology contributes to monitoring and identifying emerging outbreaks.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309124","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}
{"title":"H13N8 and H16N3 AIV Isolated From Shorebirds Can Replicate in the Rectum of Mice","authors":"Jiaqi Lan, Lanlan Liu, Xiang Li, Ru Ding, Jiali Zhu, Fengyi Qu, Boyu Zhai, Jinyan Wu, Yajun Wang, Siyuan Yang, Hongliang Chai, Xiangwei Zeng","doi":"10.1002/jmv.70455","DOIUrl":"https://doi.org/10.1002/jmv.70455","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate the pathogenicity and cross-species transmission potential of H13 and H16-subtype of low pathogenic avian influenza viruses (LPAIVs), two strains of H13N8 and H16N3 isolated from shorebirds were used to infect mice. Clinical signs were observed, and viral loads and cytokine expression levels were measured. The results showed that both H13N8 and H16N3 AIV exhibited low pathogenicity in mice and could replicate efficiently in the rectum of mice without prior adaptation. Compared with the PBS group, six cytokines were expressed at low levels, further confirming the low pathogenicity of the H13N8 and H16N3 strains in mice. The results indicate that both strains have the potential for cross-species transmission to mammals.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300439","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}
Yingnan You, Kaiyin Guo, Mengjie Ma, Xiuyun Duan, Yaxue Xie, Yanjie Jiang, Hailin Jia, Bo Han
{"title":"Single-Cell RNA Sequencing Reveals Macrophage–Endothelial Cell Crosstalk in Viral Myocarditis","authors":"Yingnan You, Kaiyin Guo, Mengjie Ma, Xiuyun Duan, Yaxue Xie, Yanjie Jiang, Hailin Jia, Bo Han","doi":"10.1002/jmv.70440","DOIUrl":"https://doi.org/10.1002/jmv.70440","url":null,"abstract":"<div>\u0000 \u0000 <p>Viral myocarditis is characterized by inflammatory cell infiltration and myocardial damage. However, the involvement of immune cells and the interaction between immune cells and stromal cells remain poorly understood. We successfully established a mouse model of viral myocarditis induced by Coxsackievirus B3 (CVB3) and systematically analyzed immune cell infiltration and myocardial injury at different time points. Single-cell RNA sequencing (scRNA-seq) was performed at the peak of immune cell infiltration to characterize the immune landscape of infected cardiac tissue and peripheral blood mononuclear cells (PBMCs). Macrophage depletion and vascular endothelial growth factor receptor (VEGFR) inhibition were performed to validate the immune-stromal crosstalk. Peak immune cell infiltration and myocardial injury occurred on the 7th day of infection. scRNA-seq revealed that endothelial cells and mononuclear phagocytes (MNPs) were the most substantially expanded cell populations in the hearts of mice with viral infection. Trem2 macrophage, characterized by tissue repair gene signatures, was the predominant MNP subcluster in the infected heart, while tip cells and capillaries were the most expanded endothelial cell clusters. Cell–cell communication analysis identified increased macrophage–endothelial cell interactions during CVB3 infection. Macrophage-derived VEGFA secretion, partially induced by CVB3 infection and apoptotic cardiomyocyte debris, promoted angiogenesis, while macrophage depletion resulted in reduced VEGFA secretion and endothelial proliferation. Moreover, inhibition of VEGFR exacerbated cardiac dysfunction, highlighting the protective role of angiogenesis in myocarditis progression. In summary, these results elucidated a cardioprotective role of macrophage-driven angiogenesis via vascular endothelial growth factor signaling during viral myocarditis, providing new insights into therapeutic strategies for inflammatory heart diseases.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300440","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":"Molecular Epidemiology of Sapovirus Infection in Japanese Children With Acute Gastroenteritis Before and After the COVID-19 Pandemic","authors":"Shoko Okitsu, Pattara Khamrin, Toshiyuki Hikita, Yuko Onda, Sheikh Ariful Hoque, Satoshi Hayakawa, Shihoko Komine-Aizawa, Niwat Maneekarn, Hiroshi Ushijima","doi":"10.1002/jmv.70450","DOIUrl":"https://doi.org/10.1002/jmv.70450","url":null,"abstract":"<div>\u0000 \u0000 <p>Sapovirus (SaV) is one of the pathogens associated with sporadic acute gastroenteritis in infants and children, and also with foodborne outbreaks in all age groups. This study investigated the molecular detection and characterization of SaV in Japanese children with acute gastroenteritis from July 2017 to June 2024, and the results were compared with those of the previous study conducted in 2014–2017. The study period of this study encompassed the period before, during, and after the COVID-19 pandemic in Japan. During the COVID-19 pandemic, both the number of collected samples and SaV-positive samples decreased remarkably. Among 931 samples included in this study, the rate of SaV infection was 7.5% (70/931), which was higher than the previous study at 5.0%, especially the rates of infection after the pandemic increased to 9.8% in 2022–2023 and 16.4% in 2023–2024. Regarding the SaV genotype distribution, GI.1 was the most predominant genotype at 37.1% comparable to those of the previous study during 2014–2017, followed by GII.3, GI.2, GII.1, GII.2 and GIV.1, GV.1, and GII.5 genotypes. In 2022–2023, GII.3 instead of GI.1 was the most common genotype; however, GI.1 resumed the most dominant genotype again the following year. The findings suggested that SaV infection in Japanese children was remarkable after the COVID-19 pandemic, and the systematic surveillance should be conducted continuously in Japan.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291890","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}
Alicia Avenhaus, Bianca J. Kuhn, Milica Velimirović, Tobias D. Strobel, Julia Bulkescher, Claudia Lohrey, Jeroen Krijgsveld, Felix Hoppe-Seyler, Karin Hoppe-Seyler
{"title":"Pleiotropic Effects of Metformin on the Chemotherapy Response of HPV-Positive Cancer Cells","authors":"Alicia Avenhaus, Bianca J. Kuhn, Milica Velimirović, Tobias D. Strobel, Julia Bulkescher, Claudia Lohrey, Jeroen Krijgsveld, Felix Hoppe-Seyler, Karin Hoppe-Seyler","doi":"10.1002/jmv.70434","DOIUrl":"https://doi.org/10.1002/jmv.70434","url":null,"abstract":"<p>Improved treatment strategies for HPV-positive cancers are urgently required. The viral E6/E7 oncoproteins are essential for the proliferation of HPV-positive cancer cells and considered attractive therapeutic targets. Metformin is proposed to be repurposed for cancer therapy, but this is under controversial debate. We previously demonstrated that E6/E7 expression and the proliferation of HPV-positive cancer cells are repressed by Metformin. Here, we explore the effects of Metformin on the phenotype of HPV-positive cancer cells in detail, either applied as monotreatment or in combination with chemotherapeutic agents. We provide evidence that the downregulation of E6/E7 is not the primary mechanism underlying Metformin's growth-inhibitory effect in HPV-positive cancer cells. Specifically, compared to targeted E6/E7 repression by RNA interference (RNAi), Metformin treatment differently altered the expression of growth regulatory proteins, exerted different effects on the cell cycle, and was able to suppress growth even in the presence of E6/E7. Furthermore, we found that cancer cells pre-treated with Metformin become resistant to senescence induction by the pro-senescent chemotherapeutic agent Etoposide, likely as a secondary effect of Metformin-induced growth inhibition. Finally, depending on experimental conditions, we uncover divergent, even opposing, effects on the proliferation of HPV-positive cancer cells when Metformin is combined with Cisplatin, with p53 playing a key role in these processes. Collectively, our results show that Metformin exerts complex effects on the phenotype of HPV-positive cancer cells, which are critically influenced by experimental conditions. Our findings may also explain the discrepant results in the literature, reporting agonistic or antagonistic effects upon combining Metformin with Cisplatin.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299683","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}
Florence Lemaitre, Clara Chivasso, Laurent Debaisieux, Marie-Hélène Jurion, Marie-Luce Delforge
{"title":"Molecular Characterization of Parvovirus B19 in Pregnant Women During the 2024 Outbreak in Belgium","authors":"Florence Lemaitre, Clara Chivasso, Laurent Debaisieux, Marie-Hélène Jurion, Marie-Luce Delforge","doi":"10.1002/jmv.70443","DOIUrl":"https://doi.org/10.1002/jmv.70443","url":null,"abstract":"<div>\u0000 \u0000 <p>Since the beginning of 2024, several countries in Europe have faced an increase in the detection of <i>Parvovirus B19</i> (B19V). The present study aimed to investigate the B19V outbreak in Belgium, focusing on molecular features and transmission dynamics among pregnant women. A total of 86 biological samples collected all over the country during the period between January and October 2024 were tested for B19V, and positive ones (<i>n</i> = 35) were used for molecular sequence investigations. An abnormal resurgence of B19V infections was first documented in February, and a significant decline was observed in October 2024. Phylogenetic analysis of all 35 sequences covering the nonstructural protein 1 (NS1)/capsid viral protein 1 (VP1) unique region junction showed that the genotype was 1a, which was in line with global patterns. The data showed that Belgian sequences clustered with strains from neighboring countries, indicating widespread circulation. The hypothesis involves the COVID-19 pandemic, which may have contributed to this outbreak, creating an immunity gap. This study highlights the importance of monitoring B19V, especially for high-risk groups, accentuating the importance of laboratory confirmation. Based on the results obtained, it is very unlikely that B19's emerging molecular features are responsible for the detection of an increasing number of cases in Belgium.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291891","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}