{"title":"Lactate Dehydrogenase/Albumin to Urea Ratio: A Novel Prognostic Indicator for Adverse Outcomes in Patients With Severe Fever With Thrombocytopenia Syndrome","authors":"Ruihua Zhang, Yameng Mu, Mengyuan Zhang, Hongxiao Wu, Yanli Xu, Chenxi Zhao, Zishuai Liu, Ling Lin, Wei Zhang, Yaxian Kong, Zhihai Chen","doi":"10.1002/jmv.70428","DOIUrl":"https://doi.org/10.1002/jmv.70428","url":null,"abstract":"<p>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with significant mortality risks. This study evaluated the predictive value of the lactate dehydrogenase/albumin to urea ratio (LAU) for lethal outcomes in SFTS patients. Clinical data from 348 patients (295 survivors, 53 non-survivors) admitted to Yantai Infectious Disease Hospital (2022-2023) were analyzed. Multivariate analysis identified older age, SFTS-associated encephalopathy, SFTSV RNA, decreased albumin and serum calcium, increased lactate dehydrogenase, and elevated LAU as independent mortality risk factors. LAU demonstrated strong predictive accuracy (AUC: 0.79; 95% CI: 0.72-0.85; sensitivity 69%, specificity 75%), with an optimal cutoff of 144.685 U·mmol/g·L. Survival analysis linked high LAU to poor prognosis, and longitudinal trends showed decreasing LAU with recovery in survivors but rising levels in non-survivors. These findings highlight LAU as a novel, practical biomarker for early risk stratification and prognosis improvement in SFTS.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220427","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}
Masoud Rahmati, Raphael Udeh, Jiseung Kang, Xenia Dolja-Gore, Mark McEvoy, Abdolreza Kazemi, Pinar Soysal, Lee Smith, Tony Kenna, Guillaume Fond, Bastien Boussat, Duy Cao Nguyen, Huyen Do, Bach X. Tran, Nicola Veronese, Dong Keon Yon, Laurent Boyer
{"title":"Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection","authors":"Masoud Rahmati, Raphael Udeh, Jiseung Kang, Xenia Dolja-Gore, Mark McEvoy, Abdolreza Kazemi, Pinar Soysal, Lee Smith, Tony Kenna, Guillaume Fond, Bastien Boussat, Duy Cao Nguyen, Huyen Do, Bach X. Tran, Nicola Veronese, Dong Keon Yon, Laurent Boyer","doi":"10.1002/jmv.70429","DOIUrl":"https://doi.org/10.1002/jmv.70429","url":null,"abstract":"<p>The symptoms of long COVID are well-documented. However, the long-term effects beyond 2 years remain poorly understood due to a lack of data. This systematic review and meta-analysis examined the prevalence of persistent symptoms in COVID-19 survivors 3 years following initial SARS-CoV-2 infection. PubMed, MEDLINE (Ovid), CENTRAL, Web of Science, Scopus, and Embase were searched from inception of the databases up to July 20, 2024, by two independent researchers for articles reporting on the prevalence of persistent symptoms 3 years' post-infection of people who survived COVID-19 infection. We employed a random-effect model for the pooled analysis, and the meta-analytical effect size was prevalence for the applicable end-points, <i>I</i><sup>2</sup> statistics, and quality assessment of included studies using the Newcastle-Ottawa Scale. Eleven articles were included after the literature search yielded 223 potentially relevant articles. We found that among patients with long COVID, fatigue, sleep disturbances, and dyspnea were the most common symptoms. Pooled analysis showed that the proportion of individuals experiencing at least one persistent symptom 3 years post-COVID-19 is 20% (95% confidence interval [CI]: 8–43). The prevalence of persistent symptoms was dyspnea (12%; 95% CI: 10–15), fatigue (11%; 95% CI: 6–20), insomnia (11%; 95% CI: 2–37), loss of smell (7%; 95% CI: 5–8), loss of taste (7%; 95% CI: 3–16), and anxiety (6%; 95% CI: 1–32). Prevalence of other findings include impaired diffusion capacity (42%; 95% CI: 34–50) and impaired forced expiratory volume in 1 s (10%; 95% CI: 8–12). Our findings confirm the persistence of unresolved symptoms 3 years post-COVID-19 infection, with implications for future research, healthcare policy, and patient care.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220426","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}
Qian Liu, Huan Wang, Xianglin Xuan, Haoyi Liu, Bizhen Tang, Zhichao Zhou, Li Zhang, Shuyan Qiu, Xiao Li, Xingui Tian, Rong Zhou, Wenkuan Liu
{"title":"Construction and In Vitro and In Vivo Analysis of Coxsackievirus B4 Reporter Viruses: Attenuated Virulence but Highly Efficient for Antiviral Drug Screening and Evaluation","authors":"Qian Liu, Huan Wang, Xianglin Xuan, Haoyi Liu, Bizhen Tang, Zhichao Zhou, Li Zhang, Shuyan Qiu, Xiao Li, Xingui Tian, Rong Zhou, Wenkuan Liu","doi":"10.1002/jmv.70433","DOIUrl":"https://doi.org/10.1002/jmv.70433","url":null,"abstract":"<div>\u0000 \u0000 <p>Coxsackievirus B4 (CVB4) is an enterovirus with one of the highest mortality rates following infection, yet research on it remains limited. To enhance the efficiency of CVB4 research, we developed the rCVB4-EGFP and rCVB4-NanoLuc reporter viruses. The replication kinetics of these reporter viruses in SH-SY5Y and HeLa cells were essentially consistent with those of the wild-type CVB4. A strong correlation was observed between the fluorescence and bioluminescence signals of rCVB4-EGFP and rCVB4-NanoLuc and viral titers at specific times postinfection. When evaluating the anti-CVB4 drug fluoxetine using these reporter viruses, the half-maximal effective concentrations derived from fluorescence signals, bioluminescence signal intensities, and viral genome copies were consistent. In In Vivo drug evaluations, because CVB4 can infect various tissues and organs, the bioluminescence signal of rCVB4-NanoLuc effectively demonstrated the antiviral effects of drugs, offering significant advantages over traditional tissue viral titer analysis. The reporter viruses exhibited reduced virulence compared with wild-type CVB4 both In Vitro, in SH-SY5Y and HeLa cells, and In Vivo, in ICR suckling mice. Although this reduced virulence may limit their application for studying pathogenic mechanisms, these reporter viruses can serve as highly efficient tools for high-throughput screening and evaluation of anti-CVB4 drugs, vaccines, and neutralizing antibodies.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220428","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}
Warittha Tieosapjaroen, Arron Tran, Marcus Maisano, Cham-mill Kim, Christopher K. Fairley, Eric P. F. Chow, Lei Zhang, Tiffany R. Phillips, Melanie Bissessor, Jason J. Ong
{"title":"Trend and Associated Factors for Late and Advanced HIV Diagnoses in 2011–2022 in Melbourne, Australia","authors":"Warittha Tieosapjaroen, Arron Tran, Marcus Maisano, Cham-mill Kim, Christopher K. Fairley, Eric P. F. Chow, Lei Zhang, Tiffany R. Phillips, Melanie Bissessor, Jason J. Ong","doi":"10.1002/jmv.70430","DOIUrl":"https://doi.org/10.1002/jmv.70430","url":null,"abstract":"<p>Late- and advanced HIV diagnoses remain significant challenges worldwide. Understanding the factors associated with and testing practice among those with late (CD4 < 350 cells/µL) and advanced diagnoses (CD4 < 200 cells/µL) is essential to diminish AIDS-related morbidity and mortality. This retrospective study manually reviewed e-medical records of new HIV diagnoses between 2011 and 2022 at Melbourne Sexual Health Centre, Australia. Among 606 new diagnoses, 25% (152/606) were late, 11% (65/606) were advanced, and 94% (568/606) were men who have sex with men. Among 352 overseas-born individuals, late or advanced diagnoses increased from 22% (4/18) in 2011 to 56% (5/9) in 2022. No significant change was observed among Australian-born individuals. Late diagnoses were associated with being born in Latin America or in East Asia and Pacific, having no prior sexually transmitted infection (STI) diagnosis in their lifetime, and no drug use in their lifetime. Advanced diagnoses were associated with being born in East Asia and the Pacific, having no prior STI, older age, Medicare-ineligibility, and unknown condom use history in the last year. Key barriers to earlier testing included LGBT-related stigma (<i>n</i> = 41) and recent arrival (< 5 years) in Australia (<i>n</i> = 41). The primary risk for contracting HIV was condomless anal sex (<i>n</i> = 80). To conclude, one in three new HIV diagnoses was late or advanced, with increased risk among overseas-born, Medicare-ineligible or those with perceived low risk. Tailored campaigns for these underserved populations are urgently needed to promote timely HIV testing.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206773","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}
Jae E. Lee, Hyesu Jo, Hanseul Cho, Jiyeon Oh, Yi Deun Jeong, Sooji Lee, Jaeyu Park, Hyeon Jin Kim, Yejun Son, Soeun Kim, Hayeon Lee, Louis Jacob, Damiano Pizzol, Ho Geol Woo, Jiyoung Hwang, Dong Keon Yon
{"title":"Global and Regional Burden of Vaccine-Associated Transverse Myelitis and Potentially Associated With Vaccines From 1967 to 2023: An Analysis of the International Pharmacovigilance Data","authors":"Jae E. Lee, Hyesu Jo, Hanseul Cho, Jiyeon Oh, Yi Deun Jeong, Sooji Lee, Jaeyu Park, Hyeon Jin Kim, Yejun Son, Soeun Kim, Hayeon Lee, Louis Jacob, Damiano Pizzol, Ho Geol Woo, Jiyoung Hwang, Dong Keon Yon","doi":"10.1002/jmv.70408","DOIUrl":"https://doi.org/10.1002/jmv.70408","url":null,"abstract":"<div>\u0000 \u0000 <p>Limited data on the potential safety risk of vaccine-associated transverse myelitis (TM) is available. Thus, we aimed to identify the global burden and clinical features of vaccine-associated TM to facilitate tailored monitoring of potential adverse vaccine reactions. This study used data from the World Health Organization pharmacovigilance database, which contains over 35 million reports from over 140 countries. We extracted individual case safety reports from 1967 to 2023. To investigate the potential association between 19 vaccines and TM, we calculated global reporting counts, reported odds ratios (ROR) with 95% confidence intervals (CI), and information components (IC) with IC<sub>0.25</sub> based on the Bayesian model. We identified 2305 reports (male, <i>n</i> = 999 [43.34%]) of vaccine-associated TM from 4007 reports of all-cause TM. Since the first report in 2010, the cumulative number of vaccine-associated TM reports has steadily increased, with a significant increase after 2020 due to the emergence of COVID-19 mRNA vaccines. Most vaccines were associated with TM (ROR, 42.62 [95% CI, 28.02–64.82]; IC, 4.46 [IC<sub>0.25</sub>, 3.75]), albeit with varying levels of signal. Typhoid vaccines had the highest signal with TM reports (ROR, 42.62 [28.02–64.82]; IC, 4.46 [3.75]), followed by hepatitis A (ROR, 38.04 [30.13–48.03]; IC, 4.90 [4.51]), influenza (ROR, 31.55 [28.17–35.32]; IC, 4.80 [4.62]), encephalitis, papillomavirus, and hepatitis B vaccines. Age- and sex-specific analyses indicated that the risk of vaccine-associated TM increased with age and to be more susceptible among males through ROR. The rate of fatal adverse outcomes of vaccine-associated TM was 0.22%. This study highlights a potential signal detection between vaccines and the onset of TM, with vaccine-associated reports comprising over half of all reported TM cases in the database. Although the incidence remains low, clinicians should remain vigilant for TM symptoms following vaccination, particularly in older adults where the risk appears to be higher. While our findings do not permit for causal inference, given the increasing trend of vaccine-associated TM reports after 2020, continued pharmacovigilance and further research are needed to ensure timely detection and management of potential risks while maintaining the benefits of immunization.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190658","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}
Jing Yu, Yong Ju, Doh Kyung Kim, Audrey Qian, Bin Du, Na Liu, Zhiyun Wei
{"title":"Changes in the Epidemiology of High-Risk HPV Genital Tract Infections Among Women in Shanghai: A Pre- and Post-COVID-19 Pandemic Analysis (2013–2024)","authors":"Jing Yu, Yong Ju, Doh Kyung Kim, Audrey Qian, Bin Du, Na Liu, Zhiyun Wei","doi":"10.1002/jmv.70424","DOIUrl":"https://doi.org/10.1002/jmv.70424","url":null,"abstract":"<div>\u0000 \u0000 <p>High-risk human papillomavirus (hrHPV), primarily transmitted through sexual contact, is a key etiological factor in cervical and other related malignant tumors, as well as their precancerous lesions. This retrospective study was conducted on clinical data from 469 775 women who underwent genital tract hrHPV testing between 2013 and early 2024. The weighted hrHPV positivity rate declined from a peak of 24.86% in 2013 to 12.25% during the COVID-19 pandemic (2020–2022) but rebounded to 17.54% in 2023 and 19.47% by early 2024 in the post-pandemic period. The three most commonly detected genotypes were hrHPV52 (4.52%), hrHPV58 (3.11%), and hrHPV16 (2.72%). Based on the overall data analysis, hrHPV positivity rates exceeded 20% in both younger (≤ 25 years) and older (≥ 50 years) age groups, while the middle-aged group (26–50 years) accounted for approximately 70% of cases. Notably, the proportion of hrHPV-positive cases exhibited a significant increasing trend among women aged ≥ 66 years throughout the study period. These findings reveal a post-pandemic rebound of hrHPV infections, highlighting the urgent need for sustained surveillance and age-specific prevention strategies to mitigate infection risk and reduce the burden of associated diseases.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190936","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":"Proteome Profiling in Cerebrospinal Fluid Reveals Increased Levels of Peroxiredoxin 2 Discriminating Japanese Encephalitis Virus and Scrub Typhus Infection","authors":"Naina Soni, Rashmi Rameshwari, Ankit Biswas, Prasanjit Jena, Tushar K. Maiti, Bishal Gupta, Bhaswati Bandyopadhyay, Arup Banerjee","doi":"10.1002/jmv.70427","DOIUrl":"https://doi.org/10.1002/jmv.70427","url":null,"abstract":"<div>\u0000 \u0000 <p>Japanese encephalitis virus (JEV) and scrub typhus (ST) are major etiological agents of acute encephalitis syndrome (AES) in India and South Asia. The pathophysiological changes at the molecular level caused by JEV and ST have yet to be studied in detail. The cerebrospinal fluid (CSF) proteomic landscape is a critical indicator of CNS pathology. Here, we conducted label-free quantitative proteomics on CSF from AES patients (<i>n</i> = 15) to identify etiology-specific differentially expressed proteins (DEPs) linked to encephalitis. The key DEPs were validated via ELISA in CSF (<i>n</i> = 49) and serum (<i>n</i> = 33). Our findings revealed 50 proteins exhibited differential expression across JEV and ST groups, with a notable subset of three proteins, PRDX2, KLK6, and TTR. PRDX2 and KLK6 were markedly elevated in JEV CSF (AUC: 0.8933 and 0.9689) but not in ST or non-JEV AES, while TTR was reduced in JEV yet elevated in ST (AUC: 0.5619 vs. 0.8238). Further, PRDX2 upregulation was validated in JEV-infected mouse brains and cortical neurons. Overexpression of PRDX2 in human neuroblastoma cells correlated with enhanced antiviral gene expression, p-STAT1, p-AKT (ser473), and viral replication. Thus, our comprehensive proteomic analysis of CSF identifies PRDX2 as an important circulatory protein, differentially expressed between JEV and ST, with high specificity and enhancing viral propagation, underscoring its role in viral propagation and pathogenesis.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197289","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":"Integrating Enzyme-DNA Complex and CRISPR/Cas12a for Robust Norovirus Detection","authors":"Junhua Wu, Qiyan Yan, Haiyan Qiu, E-Bin Gao","doi":"10.1002/jmv.70426","DOIUrl":"https://doi.org/10.1002/jmv.70426","url":null,"abstract":"<div>\u0000 \u0000 <p>Human norovirus (NoV) is a primary cause of acute gastroenteritis in children, making accurate and rapid detection essential for effective disease prevention and control. In this study, we developed a sensitive and efficient platform for pathogen nucleic acid detection by integrating asymmetric nucleic acid sequence-based amplification (asymmetric NASBA), enzyme-DNA molecular complex, and the clustered regularly interspaced short palindromic repeats (CRISPR) system, namely an A-enDMC platform. The target recognition capability of the enzyme-DNA complex operates independently from the signal amplification function of the CRISPR system. By decoupling the CRISPR reaction from the dependence on specific target sequences, the platform's universality and modularity are enhanced. The assay is fast (< 1.5 h), highly sensitive (< 5 copies/µL), and demonstrates no cross-reactivity with other common viruses. Compared to the widely used RT-qPCR method, the platform demonstrates high consistency in detection results, with the detection coincidence rate of 96.77% and a kappa value of 0.87. This platform provides a versatile technological tool for highly sensitive and specific RNA detection, demonstrating its extensive potential in real sample analysis.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190935","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}
Seungyeon Lee, Nang Kyeong Lee, Seung Won Lee, Yong Joon Kim
{"title":"Changes in the Nationwide Incidence of Bell's Palsy in the General Population Before and After the COVID-19 Pandemic: An Ecological Study","authors":"Seungyeon Lee, Nang Kyeong Lee, Seung Won Lee, Yong Joon Kim","doi":"10.1002/jmv.70431","DOIUrl":"https://doi.org/10.1002/jmv.70431","url":null,"abstract":"<p>This nationwide population-based ecological study investigated changes in the incidence of Bell's palsy (BP) in South Korea during the COVID-19 pandemic. Patients diagnosed with BP between January 2017 and December 2022 were analyzed. Considering the unique progression of the COVID-19 pandemic and corresponding public health responses in South Korea, the study period was divided into four phases: pre-COVID-19 (2017–2019), non-pharmaceutical intervention (NPI, 2020), nationwide vaccination (2021), and nationwide infection (2022). Poisson regression was used to calculate incidence rate ratios (IRRs) for each pandemic phase compared to the pre-COVID-19 baseline, adjusting for age and sex. Among 103 482 patients, BP incidence significantly decreased during the vaccination (IRR 0.96; 95% CI, 0.94–0.98) and infection (IRR 0.95; 95% CI, 0.93–0.97) phases (<i>p</i> < 0.001). These trends were more pronounced among women and older adults and did not correlate with national vaccination or infection rates. Our findings suggest that the incidence of BP did not increase during the COVID-19 era at the level of the general population nationwide. Further studies using individual-level data on COVID-19 infection and vaccination are needed to clarify their potential direct impact on BP incidence.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190937","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}
Milica Velimirović, Alicia Avenhaus, Claudia Lohrey, Julia Bulkescher, Felix Hoppe-Seyler, Karin Hoppe-Seyler
{"title":"Hypoxic HPV-Positive Cancer Cells Are Particularly Sensitive to the Pro-Senescent Effects of B-MYB Repression Due to the Lack of Compensatory A-MYB Induction","authors":"Milica Velimirović, Alicia Avenhaus, Claudia Lohrey, Julia Bulkescher, Felix Hoppe-Seyler, Karin Hoppe-Seyler","doi":"10.1002/jmv.70422","DOIUrl":"https://doi.org/10.1002/jmv.70422","url":null,"abstract":"<p>Tumor hypoxia is typically linked to increased therapy resistance and poor prognosis of many malignancies, including HPV-positive cancers. One possible resistance mechanism is the increased resistance of hypoxic tumor cells to cellular senescence. It is thus highly interesting to identify strategies which could increase their pro-senescent susceptibility. In comparative analyses of normoxic and hypoxic HPV-positive cancer cells, we here uncover that the interconnection between B-MYB and its paralog A-MYB plays a key role for their senescence response, but shows a differential regulation under normoxia and hypoxia. In specific, we demonstrate that the pro-senescent response to B-MYB loss is counteracted by a compensatory upregulation of A-MYB under normoxia. Therefore, efficient induction of senescence in normoxic cells requires the downregulation of both B-MYB and A-MYB. Interestingly, this compensatory A-MYB induction is absent under hypoxia, rendering hypoxic cancer cells particularly sensitive to the pro-senescent effect of B-MYB repression. We further show that these regulatory effects are not confined to HPV-positive cancer cells, indicating that they could be broadly conserved between different cancer types. Collectively, our findings reveal that hypoxic cancer cells are particularly sensitive to B-MYB inhibition, which could provide a new strategy to target this therapeutically challenging cancer cell population.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 6","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171878","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}