Journal of Medical Virology最新文献

{"title":"A New Dengue Rapid Test to Simultaneously Detect All Four Dengue Virus Serotypes","authors":"Michaela Cain, Hinh Ly","doi":"10.1002/jmv.70352","DOIUrl":"https://doi.org/10.1002/jmv.70352","url":null,"abstract":"<p>Dengue virus (DENV) is an enveloped, positive- and single-stranded RNA virus belonging to the <i>Flaviviridae</i> family. The <i>Flaviviridae</i> family includes more than 70 human-disease causing pathogens, such as Zika virus, Yellow fever virus, West Nile virus, Japanese Encephalitis virus, Tick-Borne Encephalitis virus, besides DENV [<span>1</span>]. There are four antigenically distinct DENV serotypes, namely DENV-1, DENV-2, DENV-3, and DENV-4. Like many flaviviruses, DENV is an arbovirus that is primarily transmitted by the bite of infected <i>Aedes aegypti</i> mosquitoes [<span>2</span>]. DENV infection is responsible for one of the most common mosquito-borne infections, causing an estimated 100–400 million infections per year globally [<span>2</span>]. The incidence of DENV infection has risen dramatically over the past decade, with 2023 recording the highest number of cases, affecting over 80 countries [<span>3</span>]. DENV is now endemic in more than 100 countries across the Americas, Africa, Southeast Asia, and the Eastern Mediterranean and Western Pacific. The expanding geographic range of the arbovirus vector <i>Aedes aegypti</i>, driven by rising temperatures and high humidity, is putting more countries at risk [<span>4</span>].</p><p>DENV infection presents with a wide range of clinical manifestations, from asymptomatic or mild febrile illness to severe, life-threatening disease. The World Health Organization (WHO) classifies DENV infection into three categories: Dengue without warning signs, dengue with warning signs, and severe dengue (SD) [<span>5</span>]. Severe dengue can lead to increased vascular permeability and coagulopathy, resulting in complications such as hypovolemic shock, organ failure, and severe bleeding. With treatment, the mortality rate is approximately 2%–5%, but it can rise to as high as 20% without timely medical intervention [<span>6</span>].</p><p>Due to the nonspecific clinical symptoms presented during the early phase of DENV infection and the limited availability of diagnostics, DENV is often underdiagnosed in endemic regions around the world. During the early stage of infection (< 5 days), diagnosis of DENV infection relies on viral isolation, genome or antigen detection using reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative RT-PCR (qRT-PCR) [<span>7</span>]. However, these techniques require technical expertise and expensive laboratory reagents and equipment, which are often not available in resource-limited settings [<span>2</span>]. After this early stage, DENV RNA or antigens may no longer be detectable in the patient, necessitating serological antibody detection [<span>7</span>]. However, the high protein-sequence similarity among DENV serotypes and other flaviviruses can lead to antibody cross-reactivity, posing a significant challenge for accurate diagnosis [<span>2</span>].</p><p>In a recent study entitled “RT-RPA assisted CRISPR/Cas12a based one-pot rapid","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801564","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":"Effects of Different Feeding Patterns on the Gut Virome of 6-Month-Old Infants","authors":"Chunduo Pan,&nbsp;Pan Xu,&nbsp;Minli Yuan,&nbsp;Shanjie Wei,&nbsp;Yan Lu,&nbsp;Hongyan Lu,&nbsp;Wen Zhang","doi":"10.1002/jmv.70344","DOIUrl":"https://doi.org/10.1002/jmv.70344","url":null,"abstract":"<div>\u0000 \u0000 <p>The gut microbiome is essential for infant health, and in recent years, the impact of enteroviruses on infant health and disease has received increasing attention. The transmission of breast milk phages to the infant gastrointestinal tract contributes to the shaping of the infant gut virome, while breastfeeding regulates the colonization of the infant gut virome. In this study, we collected fecal samples from healthy infants and analyzed the distribution characteristics of infant viral communities by viral metagenomic analysis, and analyzed the differences in infant viral communities under different feeding practices. Our results indicate that the infant intestinal virome consists of phages and eukaryotic viruses. <i>Caudovirales</i> and <i>Microviridae</i> dominated the phage composition, and except for <i>Siphoviridae</i>, which was more predominant in the intestines of formula-fed infants, there were no significant differences in the overall abundance of other <i>Caudovirales</i> and <i>Microviridae</i> in the intestines of infants with different feeding patterns. Breastfeeding can lead to a higher diversity of infant gut viruses through vertical transmission, and a highly diverse gut virome helps maintain the maturation of the gut microbiome. This study informs the shaping of gut virome in healthy infants by breastfeeding and contributes to further research on infant gut virome characteristics and formation processes.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801563","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":"Diagnostic Accuracy of the Siriraj Portable Digital Cervicography Device Versus Standard Colposcopy for Detecting CIN2+ Lesions","authors":"Methawee Ularnwong,&nbsp;Suchanan Hanamornroongruang,&nbsp;Irene Ruengkhachorn,&nbsp;Wathirada Karnchanabanyong,&nbsp;Sompop Kuljarusnont,&nbsp;Pattama Chaopotong,&nbsp;Nida Jareemit,&nbsp;Pornprom Ittiamornlert,&nbsp;Sarocha Boonkate,&nbsp;Sirakarn Rochwipaporn,&nbsp;Vilaiwan Surapo","doi":"10.1002/jmv.70339","DOIUrl":"https://doi.org/10.1002/jmv.70339","url":null,"abstract":"<p>To improve access to colposcopy for women with abnormal cervical cancer screening results, this study evaluated the diagnostic accuracy of the internally developed Siriraj portable digital cervicography device for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2⁺) and compared its performance with standard colposcopy. Consenting eligible women underwent examination using both the Siriraj portable digital cervicography device and standard colposcopy. Images from each method were independently evaluated by a physician blinded to the other images and histology results. The primary outcome was the diagnostic performance of both methods for detecting CIN2⁺. Diagnostic accuracy was compared using Cochran's <i>Q</i> test, with a significance threshold of <i>p</i> &lt; 0.05. A total of 450 women participated, with histologically confirmed CIN2⁺ in 91 cases (20.1%), including 45 women diagnosed with cervical intraepithelial neoplasia grade 3 or worse (CIN3⁺). Incorporating colposcopic impressions, the modified Reid's colposcopic index, and the modified Swede score, the Siriraj portable digital cervicography device demonstrated a diagnostic accuracy of 81.3% for CIN2⁺, whereas standard colposcopy ranged from 79.1% to 81.6%. No significant difference in diagnostic accuracy was found among the six evaluative methods (<i>p</i> = 0.558). The Siriraj portable digital cervicography device shows promise as an alternative to standard colposcopy for detecting CIN2⁺, particularly in low-resource settings. While it enables remote evaluation by trained colposcopists, its diagnostic performance remains dependent on expert image interpretation. Standardizing biopsy protocols and integrating AI-assisted analysis could further enhance its clinical utility.</p><p><b>Trial Registration:</b> TCTR20230907004; registered on September 7, 2023; https://thaiclinicaltrials.org.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801562","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":"Impact of Tenofovir Alafenamide on Lipid Profiles in Chronic Hepatitis B Patients: Systematic Review and Meta-Analysis","authors":"Ping-Yu Hsu,&nbsp;Hui-Chen Su,&nbsp;Mi-Chia Ma,&nbsp;Chien-An Chen,&nbsp;Sin-Yi Yu,&nbsp;Yi-Ming Hua","doi":"10.1002/jmv.70331","DOIUrl":"https://doi.org/10.1002/jmv.70331","url":null,"abstract":"<div>\u0000 \u0000 <p>Tenofovir alafenamide (TAF) is widely used for chronic hepatitis B (CHB) treatment due to its improved renal and bone safety compared to tenofovir disoproxil fumarate (TDF). However, emerging evidence suggests that TAF may adversely affect lipid metabolism, raising concerns about potential cardiovascular risks. A systematic review and meta-analysis following PRISMA guidelines was conducted. Studies comparing lipid profile changes in CHB patients receiving TAF, TDF, or entecavir (ETV) were retrieved from PubMed, Cochrane, and Embase. Primary outcomes included changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Sensitivity analyses were performed to assess potential confounders, including lipid-lowering therapy. Trial sequential analysis (TSA) was used to evaluate the sufficiency of evidence. A total of 23 studies (5 RCTs, 18 observational) were included. Observational data showed significant increases in TC (MD = 10.74 mg/dL), TG (MD = 11.56 mg/dL), LDL (MD = 3.08 mg/dL), and HDL (MD = 7.51 mg/dL) with TAF versus TDF. Meta-analysis of RCTs confirmed these findings, showing TC (MD = 18.28 mg/dL), LDL (MD = 13.09 mg/dL), and HDL (MD = 4.95 mg/dL) elevations. TAF is associated with increased lipid levels, likely due to the loss of TDF's lipid-lowering effect. While its cardiovascular risk remains uncertain, clinicians should monitor lipid profiles in CHB patients on TAF, particularly those at high cardiovascular risk.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793427","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":"Hepatocyte-Enriched miRNA-193b-3p Promotes Hepatitis B Virus Replication by Dual Activation of Viral Core Promoter Activity and Autophagy Induction by Targeting IGF-1R","authors":"Yingying Deng,&nbsp;Jiaxin Zheng,&nbsp;Fahong Li,&nbsp;Hecun Zou,&nbsp;Shijun Tian,&nbsp;Zhenyu Zhao,&nbsp;Huaqing Zeng,&nbsp;Yongzhen Zhai,&nbsp;Wanyu Deng,&nbsp;Jiming Zhang,&nbsp;Mengji Lu,&nbsp;Bei Jia,&nbsp;Yong Lin","doi":"10.1002/jmv.70330","DOIUrl":"https://doi.org/10.1002/jmv.70330","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis B virus (HBV) infection is a principal cause of severe liver disease in humans and is associated with increased levels of specific serum or intracellular microRNAs (miRNAs). Among these, miR-193b-3p is a liver-enriched miRNA; however, its role in HBV replication remains unknown. This study aimed to investigate the influence of chronic HBV infection on miR-193b-3p levels in the peripheral blood and liver tissues of patients with chronic hepatitis B (CHB), evaluate the effect of miR-193b-3p on HBV replication both in vitro and in vivo, and elucidate the potential underlying mechanisms. We showed that hepatic miR-193b-3p levels in patients with CHB were significantly elevated compared with those in healthy controls. Ectopic expression of miR-193b-3p significantly enhanced HBV replication and transcription in different hepatoma cell lines. Furthermore, we identified <i>IGF-1R</i> as a direct target through which miR-193b-3p regulates HBV replication. Mechanistically, miR-193b-3p increased HBV core promoter activity via the IGF-1R/FXRα axis, thereby enhancing HBV transcription. Additionally, miR-193b-3p increased IGF-1R/Akt/MDM2/p53 signaling-mediated autophagy induction, which in turn facilitated increased HBV post-transcriptional activity. Collectively, hepatocyte-enriched miR-193b-3p exerts a proviral effect on HBV replication through dual synergistic mechanisms, offering novel insights into its role in HBV replication and potential therapeutic implications in CHB infection.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793601","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":"Obstructive Sleep Apnea and Risk of Respiratory Syncytial Viral Infection: A Retrospective Multi-Institution Cohort Study","authors":"Sunny Ssu-Yu Chen,&nbsp;Tina Ting-An Lin,&nbsp;Yi-Lin Chiang,&nbsp;Chien-Yun Chen,&nbsp;Hui-Yuan Chen,&nbsp;Yao-Min Hung,&nbsp;Renin Chang","doi":"10.1002/jmv.70323","DOIUrl":"https://doi.org/10.1002/jmv.70323","url":null,"abstract":"<div>\u0000 \u0000 <p>This retrospective cohort study evaluated the association between obstructive sleep apnea (OSA) and the risk of respiratory syncytial virus (RSV) infection and its complications using data from the TriNetX US Collaborative Database. Patients diagnosed with OSA (n = 1 061 261) and matched controls (<i>n</i> = 3 479 494) were identified via ICD-10-CM codes. Propensity score matching adjusted for 19 covariates to balance baseline characteristics. Over a follow-up period ranging from 1 day to 1 year post-index, patients with OSA demonstrated a significantly higher incidence of RSV infection (0.18% vs. 0.08%; HR: 2.194, 95% CI: 2.025–2.378, <i>p</i> &lt; 0.0001). Additionally, patients with OSA exhibited increased risks for severe RSV-related complications, including respiratory failure (HR: 1.291, 95% CI: 1.147–1.453), hospitalization (HR: 1.114, 95% CI: 1.026–1.210), and admission to critical care (HR: 1.329, 95% CI: 1.118–1.579). Sensitivity analyses confirmed the robustness of these findings across various observation periods, database subsets, study timelines, and inclusion criteria. Subgroup analyses stratified by age and gender also consistently supported the primary results. These findings suggest that OSA is associated with elevated risks of RSV infection and related severe outcomes, indicating the need for further studies to validate these results and potentially classify OSA patients as a high-risk group for RSV infection.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793602","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":"SARS-CoV-2 Membrane Protein Induces MARCHF1/GPX4-Mediated Ferroptosis by Promoting Lipid Accumulation","authors":"Pei Sun,&nbsp;Qian Liu,&nbsp;Shuofeng Yuan,&nbsp;Xin-Tao Wang,&nbsp;Ye Qiu,&nbsp;Xing-Yi Ge","doi":"10.1002/jmv.70328","DOIUrl":"https://doi.org/10.1002/jmv.70328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>The membrane protein (M), a key structural protein of SARS-CoV-2 that regulates virus assembly and morphogenesis, is involved in the pathological processes of multiple organ damage and metabolic disorders. This study aims to elucidate the mechanisms of M-mediated host ferroptosis and lipid accumulation during SARS-CoV-2 infection. Here, we detected that M protein enhances cellular sensitivity to ferroptosis. Additionally, we uncovered the pivotal role of perilipin-2 and sterol regulatory element-binding protein 1 in M-induced lipid accumulation. Xanthohumol, a cost-effective and orally available diacylglycerol acyltransferase inhibitor, alleviated triglyceride and total cholesterol accumulation, thereby counteracting the M-induced ferroptosis. Furthermore, we identified that the mitochondrial import inner membrane translocase subunit TIM23 and the mitochondrial import receptor subunit TOM20 homolog contribute to M-induced mitochondrial dysfunction. Notably, inhibiting lipid synthesis effectively reduced mitochondrial reactive oxygen species and transmembrane potential, indicating a cross-talk between lipid and ferro metabolic pathways. Mechanistically, glutathione peroxidase 4 (GPX4) interacts with SARS-CoV-2 M, leading to its subsequent degradation by the Membrane Associated Ring-CH-Type Finger 1 (MARCHF1) ubiquitin ligase. M-GPX4 interaction occurs at the R72 residue, which may represent a potential therapeutic target against SARS-CoV-2 infection. M modulates lipid accumulation and further impairs mitochondrial functions, ultimately resulting in ferroptosis through MARCHF1-GPX4 axis. Disrupting host-virus interactions along this pathway may provide a therapeutic strategy for SARS-CoV-2 infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778293","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":"Unveiling the Dynamics of SARS-CoV-2 Gamma and Delta Waves in Paraná, Brazil – Delta Displacing a Persistent Gamma Through Alternative Routes of Dispersal","authors":"Emanuele Gustani-Buss,&nbsp;Carlos Eduardo Buss,&nbsp;Carlos Alberto Oliveira de Biagi,&nbsp;Isabela Medeiros de Oliveira,&nbsp;Kamila Chagas Peronni,&nbsp;Glauco Akelinghton Freire Vitiello,&nbsp;Bárbara Luisa Fermino,&nbsp;Fernanda Ivanski,&nbsp;Bárbara Mendes Paz Chao,&nbsp;Felipe Francisco Bondan Tuon,&nbsp;Franciele Ani Caovilla Follador,&nbsp;Leia Carolina Lucio,&nbsp;Lirane Elize Defante Ferreto,&nbsp;Marcos Pillegi,&nbsp;Jeane Eliete Laguila Visentainer,&nbsp;Marcia Edilaine Lopes Consolaro,&nbsp;Maria Leandra Terêncio,&nbsp;Dennis Armando Bertolini,&nbsp;Alex Sandro Jorge,&nbsp;Jaime Luis Lopes Rocha,&nbsp;Bruno Zagonel Piovesan,&nbsp;Irina Nastassja Riediger,&nbsp;Diogo Muller Lacerda,&nbsp;Angélica Regina Cappellari,&nbsp;Marco Antonio Largura,&nbsp;Álvaro Largura,&nbsp;Patrik André Barcaro,&nbsp;Vitoria Caroline Tomacheski Schultz Bertol,&nbsp;Marcos Aurélio Pelegrina,&nbsp;Glauco Nonose Negrão,&nbsp;Carla Luiza da Silva,&nbsp;Daniela Frizon Alfieri,&nbsp;Tony Vinicius Moreira Sampaio,&nbsp;Andrea Name Colado Simao,&nbsp;Emerson Carraro,&nbsp;Wilson Araújo Silva Jr.,&nbsp;Phillippe Lemey,&nbsp;David Livingstone Alves Figueiredo","doi":"10.1002/jmv.70318","DOIUrl":"https://doi.org/10.1002/jmv.70318","url":null,"abstract":"<p>The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778292","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":"H3K27-me3 Inhibition Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts","authors":"Ram Kumar,&nbsp;Assim Verma,&nbsp;Himanshu Kamboj,&nbsp;Tarun K. Bhattacharya,&nbsp;Sanjay Barua,&nbsp;Bhupendra N. Tripathi,&nbsp;Shalini Sharma,&nbsp;Naveen Kumar","doi":"10.1002/jmv.70332","DOIUrl":"https://doi.org/10.1002/jmv.70332","url":null,"abstract":"<div>\u0000 \u0000 <p>Emerging evidence highlights the role of epigenetic modification in virus infection. In this study, inhibition of H3K27-methylation (H3K27-me3) by UNC1999 (H3K27-methyltransferase inhibitor) was demonstrated to inhibit SARS-CoV-2 replication, as evidenced by reduced levels of viral RNA/protein. The m6A modifications of SARS-CoV-2 RNA were predominantly present on the 3ʹ end, particularly the “N” gene. The methylated RNA immunoprecipitation (MeRIP) and western-blot analysis revealed a negative correlation between levels of cellular H3K27-me3 and m6A-modifications on the SARS-CoV-2 “N” gene. Moreover, m6A-modifications of the SARS-CoV-2 “N” gene were shown to promote the recruitment of YTHDF2, which eventually resulted in decay of the viral transcripts. The application of the H3K27-demethyltransferase or KDM6A/B inhibitor GSK-J4 can restore H3K27-me3 levels and mitigating the decay of viral mRNA in UNC1999-treated SARS-CoV-2-infected cells. Furthermore, long-term sequential passage (P = 50) of the virus in the presence of UNC1999 did not yield any UNC1999-resistant SARS-CoV-2 mutants. In conclusion, by integrating transcriptomics, molecular virology and functional analyses, we for the first time demonstrated that inhibition of H3K27-me3 induces m6A-mediated decay of SARS-CoV-2 transcripts, highlighting UNC1999 as novel antiviral candidate against SARS-CoV-2.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770440","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":"Myeloid-Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID-19","authors":"Cong Lai,&nbsp;Su Lu,&nbsp;Yilin Yang,&nbsp;Xiaoyu You,&nbsp;Feixiang Xu,&nbsp;Xinran Deng,&nbsp;Lulu Lan,&nbsp;Yuesheng Guo,&nbsp;Zhongshu Kuang,&nbsp;Yue Luo,&nbsp;Li Yuan,&nbsp;Lu Meng,&nbsp;Xueling Wu,&nbsp;Zhenju Song,&nbsp;Ning Jiang","doi":"10.1002/jmv.70335","DOIUrl":"https://doi.org/10.1002/jmv.70335","url":null,"abstract":"<p>The objective of this study was to better understand immune failure mechanisms during <i>severe acute respiratory syndrome coronavirus 2</i>, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities and performed high-quality single-cell TCR/BCR sequencing to analyze the peripheral immune cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments. Our integrated multiomics analysis uncovers a profound immune paradox in severe COVID-19: hyperinflammation coexists with immunosuppression, driven by distinct yet interconnected dysregulatory mechanisms. Severe patients develop robust humoral immunity, evidenced by clonally expanded plasma cells producing neutralizing antibodies (e.g., IGHG1-dominated responses) and antigen-specific T cell activation. However, these protective responses are counteracted by myeloid-driven immunosuppression, particularly <i>CD14</i>+ <i>HMGB2+</i> monocytes exhibiting metabolic reprogramming and HLA-DR downregulation, coupled with progressive T cell exhaustion characterized by IFN-γ/TNF-α hyperactivation and impaired antigen presentation. Importantly, prolonged viral persistence in severe cases arises from a failure to coordinate humoral and cellular immunity—antibody-mediated neutralization cannot compensate for defective cytotoxic T cell function and monocyte-mediated immune suppression. These findings highlight the necessity for therapeutic strategies that simultaneously enhance antibody effector functions (e.g., Fc optimization), restore exhausted T cells, and reverse myeloid suppression. They also highlight the importance of vaccines designed to elicit balanced B cell memory and durable T cell responses, which are critical to preventing severe disease progression. By addressing the dual challenges of hyperinflammation and immunosuppression, such approaches could restore immune coordination and improve outcomes in severe COVID-19.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770185","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}