Journal of Medical Virology最新文献_第4页

A Pyrido-Quinoxaline Derivative That Downregulates Reticulon 3 Protein Exhibits Potent Antiviral Activity Against Zika Virus 吡喹诺啉衍生物下调Reticulon 3蛋白显示对寨卡病毒有效的抗病毒活性。

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-18 DOI: 10.1002/jmv.70605

Erika Plicanti, Andrea Deiana, Silvia Nottoli, Giulia Lottini, Roberta Ibba, Sandra Piras, Carlo Di Marzo, Silvia Vegni, Michele Lai, Mauro Pistello, Antonio Carta, Giulia Freer

{"title":"A Pyrido-Quinoxaline Derivative That Downregulates Reticulon 3 Protein Exhibits Potent Antiviral Activity Against Zika Virus","authors":"Erika Plicanti, Andrea Deiana, Silvia Nottoli, Giulia Lottini, Roberta Ibba, Sandra Piras, Carlo Di Marzo, Silvia Vegni, Michele Lai, Mauro Pistello, Antonio Carta, Giulia Freer","doi":"10.1002/jmv.70605","DOIUrl":"10.1002/jmv.70605","url":null,"abstract":"<p>In the wake of the COVID-19 pandemic, awareness of emerging pathogens has significantly increased, prompting greater investment in research and preparedness. In this context, arboviral diseases are recognized as unmet medical challenges due to their rapid spread. Notably, the geographical range of several flaviviral diseases is expanding: Zika virus (ZIKV), a member of the <i>Flaviviridae</i> family, has recently been linked to outbreaks associated with a rise in microcephaly cases in tropical regions. To contribute to the development of novel antiviral therapies, evaluation of a set of compounds with an antiviral activity against ZIKV was carried out. These compounds were originally identified as inhibitors of bovine viral diarrhea virus, another member of the <i>Flaviviridae</i> family. Two related compounds turned out to be active against ZIKV. One emerged as a particularly strong antiviral candidate, demonstrating high efficacy in inhibiting ZIKV replication, and became the focus of this study. Its activity was tested against a number of viruses of human health relevance and the compound was found to be effective against a number of viruses that use the endoplasmic reticulum as a replication hub. Indeed, we found that the Reticulon 3 protein is potently downregulated in the presence of the compound, whereas other endoplasmic reticulum-resident proteins are not affected. Because Reticulon 3 has a role in the replication of positive-sense single-stranded RNA viruses, an indirect antiviral effect of the compound studied was hypothesized. This compound may be considered as a promising lead for further studies aimed at the development of broad-spectrum antiviral drugs.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086314","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}

引用次数: 0

Virus–Host Interaction: Investigating Novel Transcription Factors Involved in Coupling Human Papillomavirus Life Cycle and Epithelial Differentiation 病毒与宿主的相互作用：研究人类乳头瘤病毒生命周期与上皮分化耦合的新型转录因子。

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-17 DOI: 10.1002/jmv.70610

Aline L. Ribeiro, Valéria Talpe-Nunes, Amanda S. Caodaglio, Rafaella A. L. Nunes, João S. P. Sobrinho, Laura Sichero

{"title":"Virus–Host Interaction: Investigating Novel Transcription Factors Involved in Coupling Human Papillomavirus Life Cycle and Epithelial Differentiation","authors":"Aline L. Ribeiro, Valéria Talpe-Nunes, Amanda S. Caodaglio, Rafaella A. L. Nunes, João S. P. Sobrinho, Laura Sichero","doi":"10.1002/jmv.70610","DOIUrl":"10.1002/jmv.70610","url":null,"abstract":"<p>High-risk human papillomavirus (HPV) is the etiological agent of nearly all cervical cancers, with HPV-18 being the second most prevalent type. The HPV life cycle is closely associated with epithelial differentiation, a process governed by cellular transcription factors (TFs). During progression toward malignancy, HPV disrupts differentiation and promotes uncontrolled cell proliferation. We aimed to identify differentiation-modulated TFs linking viral transcription to differentiation, providing insights into mechanisms driving viral life cycle and pathogenesis. DNA-binding activity of 345 TFs was compared between undifferentiated and differentiated keratinocytes to identify differentiation-associated TFs. In silico analyses identified putative binding sites for these TFs within the HPV-18 long control region (LCR). Chromatin immunoprecipitation confirmed direct binding of PAX6, HMGB1, and NFE2 to the LCR, but not FOXI1. Immunohistochemistry in keratinocyte raft cultures demonstrated differentiation-dependent expression patterns for all four TFs. Functional assays revealed that each TF is capable of modulate HPV-18 early promoter activity, with effects varying by differentiation status. Notably, expression of these TFs was disrupted by the viral oncoproteins E6 and E7, underscoring a mechanism by which HPV alters host differentiation. These findings identify novel differentiation-linked regulators of HPV-18 transcription and highlight host targets exploited by the virus in its life cycle and pathogenesis.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075385","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}

引用次数: 0

Japanese Encephalitis Virus Genotype 5 Infectious Clone and Reporter System for Antiviral Evaluation 日本脑炎病毒基因5型感染克隆及抗病毒评价报告系统

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-16 DOI: 10.1002/jmv.70608

Jae-Yeon Park, Wataru Kamitani, Hyun-Jin Shin, Hye-Mi Lee

{"title":"Japanese Encephalitis Virus Genotype 5 Infectious Clone and Reporter System for Antiviral Evaluation","authors":"Jae-Yeon Park, Wataru Kamitani, Hyun-Jin Shin, Hye-Mi Lee","doi":"10.1002/jmv.70608","DOIUrl":"10.1002/jmv.70608","url":null,"abstract":"<p>The recent emergence of Japanese encephalitis virus genotype 5 (JEV5) has raised concerns regarding limited vaccine efficacy. Here, we report the construction of a full-length infectious cDNA clone of JEV5 using a bacterial artificial chromosome (BAC) system, based on a South Korea isolate, K15P38 strain. The resulting clone enabled recovery of replication-competent virus and was genetically distinguishable from the parental strain via engineered silent mutations. To extend its application, we introduced nanoluciferase and enhanced green fluorescent protein into the viral genome, generating reporter viruses suitable for replication tracking. Both reporter viruses supported real-time quantification of viral replication and demonstrated utility in antiviral compound screening. Antiviral evaluation using the nucleoside analog NITD008 yielded EC₅₀ values consistent between reporter and classical plaque assays. These findings provide a reverse genetics platform for studying JEV5 and suggest applicability for genotype-specific vaccine and antiviral research.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069758","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}

引用次数: 0

Tracking SARS-CoV-2 Lineages in Pakistan′s 2025 COVID-19 Resurgence: Insights From Genomic Surveillance 追踪巴基斯坦2025年COVID-19卷土重来中的SARS-CoV-2谱系：来自基因组监测的见解。

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-16 DOI: 10.1002/jmv.70607

Nazish Badar, Muhammad Salman, Abdul Ahad, Hamza Ahmed Mirza

引用次数: 0

Ubiquitination: A Double-Edged Mechanism in Coronavirus Infections 泛素化：冠状病毒感染的双刃剑机制

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-14 DOI: 10.1002/jmv.70589

Sijie Liu, Chuhan Shao, Yina Ding, Yuxuan Wang, Liangyin Jin, De-an Tan, Shanni Li, Xu Deng, Yuzheng Zhou, Zanxian Xia

{"title":"Ubiquitination: A Double-Edged Mechanism in Coronavirus Infections","authors":"Sijie Liu, Chuhan Shao, Yina Ding, Yuxuan Wang, Liangyin Jin, De-an Tan, Shanni Li, Xu Deng, Yuzheng Zhou, Zanxian Xia","doi":"10.1002/jmv.70589","DOIUrl":"https://doi.org/10.1002/jmv.70589","url":null,"abstract":"<div>\u0000 \u0000 <p>The emergence of SARS-CoV-2 in late 2019 had a profound impact on public health, leading to the global COVID-19 pandemic. This viral outbreak has significantly heightened interest in coronaviruses, accelerating research into their pathogenesis. Ubiquitination, a common Posttranslational protein modification, plays a crucial role in processes such as protein localization, metabolism, and degradation. During coronavirus invasion and disease progression, complex interactions involving ubiquitination are at play. On one hand, the host utilizes ubiquitination to activate innate immune signaling pathway or degrade crucial viral proteins via the ubiquitin-proteasome pathway, thereby inhibiting viral replication. On the other hand, coronaviruses manipulate ubiquitination to suppress the activation of key antiviral molecules or promote their degradation. Thus, both the host and virus leverage ubiquitination to their advantage. Thus, investigating the role of ubiquitination in coronavirus infection provides crucial insights into viral infection mechanisms and pathogenesis, potentially facilitating the development of novel antiviral drugs, particularly those targeting ubiquitination regulation, such as PROTAC. This paper offers a comprehensive examination of the regulatory function of ubiquitination in coronavirus infection, with the potential to advance research in the field and open new avenues for the effective control of coronaviruses, especially SARS-CoV-2.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057891","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}

引用次数: 0

Summary of the 12th International Conference on Human Herpesviruses-6A, -6B, and -7 第十二届人类疱疹病毒- 6a、-6B和-7国际会议综述

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-14 DOI: 10.1002/jmv.70602

Anthony L. Komaroff, Hideo Asada, Masao Ogata, Tetsushi Yoshikawa, Yasuko Mori

{"title":"Summary of the 12th International Conference on Human Herpesviruses-6A, -6B, and -7","authors":"Anthony L. Komaroff, Hideo Asada, Masao Ogata, Tetsushi Yoshikawa, Yasuko Mori","doi":"10.1002/jmv.70602","DOIUrl":"https://doi.org/10.1002/jmv.70602","url":null,"abstract":"<div>\u0000 \u0000 <p>The 12th International Conference on Human Herpesvirus (HHV)-6A, HHV-6B, and HHV-7 was held in Himeji, Japan, from March 25 to March 27, 2025. It attracted over 120 basic, translational, and clinical scientists from 17 countries. Important new information was presented regarding: studies of viral genes and proteins; mechanism of chromosomal integration of the viral genome; host cell interactions; inherited chromosomally integrated HHV-6A/B, also called endogenous HHV-6A/B); the role of the viruses in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS); the role of the viruses as opportunistic pathogens in immunocompromised people; the role of the viruses in diseases of the central nervous system, particularly encephalopathy, post-COVID neurological conditions, complex febrile seizures, and synucleinopathies; and the possible role of the viruses in non-Hodgkin lymphoma and autoimmune diseases, including systemic lupus erythematosus. In this review, we summarize many of the oral presentations. The full text of the Conference Abstracts is available at: https://hhv-6foundation.org/wp-content/uploads/2025/06/Abstracts_FINAL-3.10.25.pdf.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057892","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}

引用次数: 0

Effectiveness of Metformin in Preventing Herpes Zoster Japanese Patients With Type 2 Diabetes: A Target Trial Emulation 二甲双胍预防日本2型糖尿病患者带状疱疹的有效性：一项目标试验模拟

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-14 DOI: 10.1002/jmv.70606

Shunsuke Hiroki, Toshiki Fukasawa, Kasumi Yokogawa, Koji Kawakami

{"title":"Effectiveness of Metformin in Preventing Herpes Zoster Japanese Patients With Type 2 Diabetes: A Target Trial Emulation","authors":"Shunsuke Hiroki, Toshiki Fukasawa, Kasumi Yokogawa, Koji Kawakami","doi":"10.1002/jmv.70606","DOIUrl":"https://doi.org/10.1002/jmv.70606","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Patients with type 2 diabetes have a higher risk of herpes zoster (HZ). Although metformin may reduce this risk via immunomodulatory effects, prior evidence is limited by confounding by indication and an unclear causal estimand. We aimed to estimate the per-protocol effect of sustained metformin use on the risk of HZ in comparison with dipeptidyl peptidase-4 (DPP-4) inhibitors, for which no evidence suggests an elevated HZ risk. We emulated a target trial using a Japanese claims database (April 2012–December 2023) to assess the 4-year risk of HZ among new users of either metformin or a DPP-4 inhibitor. Risks were estimated using an inverse probability weighted pooled logistic regression model. Among 9691 metformin users, 154 developed HZ (weighted 4-year risk: 4.18%), while among 17 202 DPP-4 inhibitor users, 345 developed HZ (4.92%). The risk difference was −0.74% (95% CI, −1.80 to 0.39), and the risk ratio was 0.85 (95% CI, 0.66 to 1.08). In conclusion, metformin use did not reduce the 4-year risk of HZ compared with DPP-4 inhibitor use. This finding contradicts a prior observational report of a marked risk reduction, which was likely inflated by confounding by indication, and highlights the need to specify a clear causal estimand.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057893","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}

引用次数: 0

Development of a HEp2-CDX Mouse Model With Sustained High RSV Viral Loads for Robust Antiviral Therapeutic Evaluation 具有持续高RSV病毒载量的HEp2-CDX小鼠模型的建立用于稳健抗病毒治疗评估

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-14 DOI: 10.1002/jmv.70601

Jinwei Yuan, Duo Xu, Xiaohong Liao, Chengxing Zhou, Qiong Zhang, Hui Liao, Minglei Liu, Zhoulang Wang, Jing Dai, Ren Cao, Qiuru Li, Hui Cai, Rong Zhou, Xingui Tian

{"title":"Development of a HEp2-CDX Mouse Model With Sustained High RSV Viral Loads for Robust Antiviral Therapeutic Evaluation","authors":"Jinwei Yuan, Duo Xu, Xiaohong Liao, Chengxing Zhou, Qiong Zhang, Hui Liao, Minglei Liu, Zhoulang Wang, Jing Dai, Ren Cao, Qiuru Li, Hui Cai, Rong Zhou, Xingui Tian","doi":"10.1002/jmv.70601","DOIUrl":"https://doi.org/10.1002/jmv.70601","url":null,"abstract":"<div>\u0000 \u0000 <p>The respiratory syncytial virus (RSV) is a predominant pathogen that causes lower respiratory tract infections and is widespread among infants and the elderly. Antibodies and antiviral drugs are effective treatment strategies for RSV, but their efficacy varies among different animal models. Here, we present a mouse model constructed using HEp-2 cell line-derived xenograft (HEp2-CDX) technology. The HEp2-CDX mouse model sustained high viral loads following both intratumoral and intravenous inoculation with RSV. The average peak titers rapidly reached 1 × 10<sup>7</sup> copies/g in lung tissues and 6 × 10<sup>9</sup> copies/g in the tumor tissues over a period up to 5 days. Furthermore, the addition of a clinical monoclonal antibody (nirsevimab) and an antiviral drug (ziresovir) showed strong antiviral activity within this animal model. These findings suggest that HEp2-CDX mice, which enable stable RSV infection and replication, serve as useful models for evaluating antiviral therapeutics.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057890","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}

引用次数: 0

Correction to “Symptoms and Risk Factors for Long Covid: A Cross-Sectional Study In Primary Care” 对“长期Covid的症状和危险因素：初级保健的横断面研究”的更正

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-12 DOI: 10.1002/jmv.70609

引用次数: 0

Heterogeneous Evolution Among SARS-CoV-2 Genes and Variants of Concern SARS-CoV-2基因及其变异的异质进化

IF 4.6 3区医学

Journal of Medical Virology Pub Date : 2025-09-12 DOI: 10.1002/jmv.70604

Luis Daniel González-Vázquez, Paula Iglesias-Rivas, David Ferreiro, Miguel Arenas

{"title":"Heterogeneous Evolution Among SARS-CoV-2 Genes and Variants of Concern","authors":"Luis Daniel González-Vázquez, Paula Iglesias-Rivas, David Ferreiro, Miguel Arenas","doi":"10.1002/jmv.70604","DOIUrl":"https://doi.org/10.1002/jmv.70604","url":null,"abstract":"<p>Challenges persist regarding the influence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on public health, with growing interest in future viral molecular variants. In this context, accurate predictions demand a thorough understanding of the virus's molecular evolution, especially proteins targeted by therapies, where certain discrepancies among studies exist. We analyzed thousands of SARS-CoV-2 genomes to assess the rate of evolution and molecular adaptation in the various SARS-CoV-2 coding regions. We found an overall low genetic diversity along the genome, with fluctuations over time and among genomic regions, and a notable increase in the Omicron variant, especially in the <i>S</i> and <i>ORF6</i> genes. We also estimated an overall rate of molecular evolution of approximately 10<sup>−3</sup> substitutions per site per year, though it varied among genomic regions and over time. Actually, most genomic regions did not follow the strict molecular clock. Regarding selective pressures, the protein-coding regions of SARS-CoV-2 generally exhibited evidence of purifying selection, with local diversifying selection associated with virus transmission and replication. Overall, the molecular evolution of SARS-CoV-2 displays heterogeneity among genomic regions and over time. These findings suggest that forecasting SARS-CoV-2 molecular evolution is not straightforward and remark the importance of continuing to monitor SARS-CoV-2 evolution.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038054","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}

引用次数: 0