Han Cao, Hui Li, Anguo Yin, Ning Luan, Chenxi Jia, Jie Song, Cunbao Liu
{"title":"A QS21+ CpG-Adjuvanted Inactivated Vaccine Elicits Superior Humoral and Moderate Cellular Immunity","authors":"Han Cao, Hui Li, Anguo Yin, Ning Luan, Chenxi Jia, Jie Song, Cunbao Liu","doi":"10.1002/jmv.71179","DOIUrl":"10.1002/jmv.71179","url":null,"abstract":"<div>\u0000 \u0000 <p>Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. Inactivated vaccines without any adjuvants are the sole vaccines licensed for the prophylaxis of rabies. We developed a novel QS21+CpG-adjuvanted inactivated vaccine and systematically compared its performance against inactivated vaccine and Alum-adjuvanted inactivated vaccine. The result shows the QS21+CpG-adjuvanted inactivated vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The QS21+CpG-adjuvanted inactivated vaccine maintained its expected cellular immunity advantage, with significantly increased frequencies of IFN-γ- and IL-2-secreting splenocytes, as well as elevated IFN-γ and IL-2 levels in splenocyte culture supernatants. Both QS21+CpG and Alum-adjuvanted inactivated vaccine groups provided 100% protection against lethal challenge. These findings provide novel adjuvant strategies for licensed inactivated rabies vaccines and offer critical insights for pathogens requiring robust humoral and Th1-biased cellular immunity.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245055","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":"Serum Golgi Protein 73 as a Noninvasive Marker of Hepatic Fibrosis in Chronic Hepatitis C Virus Infection","authors":"Yun-Chu Chen, Yu-Ping Chang, Jenna Bedrava, Laurel Jackson, Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih, Cheng-Yuan Peng, Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao, Claire Chen, Chen-Hua Liu","doi":"10.1002/jmv.71183","DOIUrl":"10.1002/jmv.71183","url":null,"abstract":"<div>\u0000 \u0000 <p>The clinical utility of serum Golgi protein 73 (GP73) for evaluating hepatic fibrosis in hepatitis C virus (HCV) infection remains to be determined. We retrospectively enrolled 978 patients with serum GP73, aspartate-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) measurements. Hepatic fibrosis was staged using vibration-controlled transient elastography (VCTE) with cutoff values of ≤ 7.0, 7.1–9.4, 9.5–12.4, and ≥ 12.5 kPa corresponding to F0–F1, F2, F3, and F4. Distributions of GP73, APRI, and FIB-4 levels across fibrosis stages were compared using Kruskal–Wallis tests. Areas under the receiver operating characteristic curves (AUROCs) were calculated and compared using DeLong tests, and optimal GP73 cutoff values were determined by maximal Youden indices. Multivariable linear regression was performed for factors associated with GP73 levels. Median GP73, APRI, and FIB-4 levels increased with advancing fibrosis stage (<i>p</i> < 0.001). Serum GP73 showed superior performance to APRI in discriminating ≥ F2 (AUROC 0.86 vs. 0.79, <i>p</i> < 0.001), ≥ F3 (0.88 vs. 0.81, <i>p</i> < 0.001), and F4 (0.90 vs. 0.84, <i>p</i> = 0.002). GP73 showed better performance than FIB-4 for ≥ F2 (0.86 vs. 0.82, <i>p</i> = 0.005) and comparable performance for ≥ F3 (0.88 vs. 0.87, <i>p</i> = 0.63) and F4 (0.90 vs. 0.89, <i>p</i> = 0.72). Optimal GP73 cutoff values were 122, 159, and 174 ng/mL for ≥ F2, ≥ F3, and F4. Regression analysis demonstrated a significant association between fibrosis stage and GP73 levels. In conclusion, serum GP73 is a reliable and accurate noninvasive biomarker for staging hepatic fibrosis for HCV.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220408","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}
Jiawei Su, Chunlian Zhai, Yuxin Li, Ruikang Liu, Jili Zhu, Kan Chen, Yanrong Zhou, Ting Ye, Gongchu Li
{"title":"Oncolytic Vaccinia Virus Armed With CLEC2A Enhances Antitumor Immunity via ROS-Autophagy Feedback Loop and Cytokine Activation","authors":"Jiawei Su, Chunlian Zhai, Yuxin Li, Ruikang Liu, Jili Zhu, Kan Chen, Yanrong Zhou, Ting Ye, Gongchu Li","doi":"10.1002/jmv.71174","DOIUrl":"10.1002/jmv.71174","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumors often exhibit immunosuppressive microenvironments (TMEs) and present as immunologically “cold.” Oncolytic viruses (OVs), particularly engineered vaccinia viruses (oncoVVs), are an encouraging therapy that directly lyses cancer cells and reprograms the TME. In this study, we evaluated the therapeutic potential of an oncolytic vaccinia virus expressing human C-type lectin domain family 2 member A (oncoVV-CLEC2A) in melanoma and ovarian cancer cells. OncoVV-CLEC2A elevated reactive oxygen species (ROS) levels, suppressed Nrf2-mediated antioxidant responses, and triggered autophagy. These changes promoted cytokine production (IL-6, IFN-α/β/γ, TNF-α) via activation of AP-1 and IRF3/7. In a B16-F10 melanoma model, oncoVV-CLEC2A increased serum levels of IFN-γ, accompanied by augmented infiltration of CD8<sup>+</sup> T cells and activation of NK cells. Taken together, oncoVV-CLEC2A reshapes the TME by intensifying oxidative stress and autophagic activity, effectively turning “cold” tumors “hot.” Notably, the mutual reinforcement between ROS production and autophagy activation not only enhances viral replication but also triggers cytokine-mediated immunity.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220453","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}
Yahui Liu, Ming Tan, Yuting Liu, Ju Kong, Xu Wen, Leirong Gu, Xiameng Su, Shengtao Cheng, Hui Zhang
{"title":"A Novel cccDNA-Binding Protein HSPA1B Promotes HBV Transcription and HBx-Mediated HCC Metastasis via Downregulating SOX4","authors":"Yahui Liu, Ming Tan, Yuting Liu, Ju Kong, Xu Wen, Leirong Gu, Xiameng Su, Shengtao Cheng, Hui Zhang","doi":"10.1002/jmv.71181","DOIUrl":"10.1002/jmv.71181","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) occurrence and progression are closely associated with hepatitis B virus (HBV) infection. Heat shock protein family A member 1B (HSPA1B), a key member of the heat shock protein 70 family, has attracted extensive attention in viral infection research, yet its specific function in HBV-related HCC pathogenesis remains largely unknown. HSPA1B was identified as a cccDNA-binding protein using the biotin-avidin system, and its role in HBV infection and HCC progression was systematically investigated. <i>In vivo</i> experiments were performed using a mouse model established by tail vein injection of prcccDNA and pCMV-KRAB-Cre to evaluate the impact of HSPA1B on HBV transcription and replication. RNA sequencing was applied to HBV-infected HepG2-NTCP cells to analyze the differentially expressed genes regulated by HSPA1B, aiming to clarify the molecular mechanism underlying HSPA1B-mediated promotion of HBV transcription and replication. Meanwhile, Western blot, RT-qPCR, co-immunoprecipitation and Transwell assays were used to explore the relationship between HSPA1B and HBV-related HCC. We found that HSPA1B promoted HBV transcription and replication. Mechanistically, the increased expression of HSPA1B promoted HBV transcription and replication by downregulating SOX4 and enhancing the stability of the HBx protein. Further research indicated that HSPA1B can enhance the metastasis and invasion of HBx-mediated HCC. Collectively, these results demonstrate a novel function of HSPA1B in regulating HBV transcription and HBV-related HCC metastasis, indicating that HSPA1B may serve as a promising therapeutic target for HBV-associated HCC.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220467","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 scRNA-Seq and Spatial Transcriptomics Reveal Novel Risk Stratification Signatures in Cervical Carcinoma","authors":"Jiayu Chen, Zhaoxiang Xie, Xuzhu Liu, Liangkai Zheng, Meiqing Li, Yanxiu Liu, Meng Jiang, Weiyan Ma, Chen Lin, Yulin Zhou, Rongqin Ke","doi":"10.1002/jmv.71184","DOIUrl":"https://doi.org/10.1002/jmv.71184","url":null,"abstract":"<div>\u0000 \u0000 <p>Cervical cancer is the fourth most common malignancy in women worldwide. Biomarker-assisted screening may improve diagnostic accuracy, but biomarkers predicting progression of low-grade squamous intraepithelial lesions (LSIL) remain limited. We integrated single-cell RNA sequencing and spatial transcriptomics to identify prognostic biomarkers associated with LSIL outcomes, followed by validation using improved in situ sequencing (IISS). Analysis of 341,978 single cells identified eight major cell populations and twelve epithelial subclusters, including a previously unrecognized subcluster, epi8. Although mainly derived from normal cervix, epi8 exhibited cancer-associated features and shared molecular characteristics with the prognostic biomarkers <i>FAM19A4</i> and <i>miR124-2</i>. <i>In situ</i> sequencing showed that epi8 localized adjacent to human papillomavirus-infected basal cells, with stage-dependent spatial changes during disease progression. Retrospective analysis further demonstrated that epi8-associated markers stratified LSIL into progression, persistence, and regression groups, with <i>CRYAB</i><sup><i>high</i></sup><i>/GAS5</i><sup><i>high</i></sup> associated with progression and <i>RPLP1</i><sup><i>high</i></sup><i>/SNHG5</i><sup><i>high</i></sup> associated with regression. We identified a previously unrecognized epithelial subcluster associated with early cervical carcinogenesis and demonstrated that its molecular markers enable risk stratification of LSIL, providing candidate biomarkers for precision triage in cervical cancer screening.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206021","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}
Fabian Ritter, Stephan Moser, Karoline Leuzinger, Michael Osthoff
{"title":"Torque Teno Virus Viremia in Complicated Staphylococcus aureus Infection: Prevalence, Viral Load, and Associations With Inflammatory Markers and Clinical Outcomes","authors":"Fabian Ritter, Stephan Moser, Karoline Leuzinger, Michael Osthoff","doi":"10.1002/jmv.71182","DOIUrl":"https://doi.org/10.1002/jmv.71182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Torque teno virus (TTV) is a recognized marker of immune competence, but its relevance in severe bacterial infections is unclear. We evaluated prevalence, viral load, and clinical relevance of TTV viremia in complicated <i>Staphylococcus aureus</i> infection (CSAI). In this ancillary analysis of two prospective pharmacokinetic cohort studies at a Swiss university hospital, stored plasma samples were tested for TTV DNA using TTV R-GENE PCR, and cytokines were measured by multiplex immunoassay. Associations between TTV load, inflammatory biomarkers, and clinical outcomes (including 30-day mortality) were assessed. Among 103 patients (median age 67.9 years; 85% with bloodstream infection), TTV viremia was detected in 76% at baseline with a median viral load of 2.85 log<sub>10</sub> copies/mL (IQR 1.87–3.56). Levels remained stable over 1 week despite declining inflammatory markers. Baseline TTV load was numerically higher in 30-day non-survivors (3.53 vs. 2.83 log<sub>10</sub> copies/mL; <i>p</i> = 0.054) and not associated with mortality after adjusting for age, sex, and SOFA score (OR 1.29 per log<sub>10</sub> increase; 95% CI 0.82–2.02; <i>p</i> = 0.268). TTV load was not associated with ICU admission, bacteremia duration, or length of stay. TTV viremia is common in CSAI but shows no significant association with inflammation or short-term outcomes, suggesting limited value for risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.71182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206030","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}
Keerthana M R, Shukla Das, Charu Jain, Pooja Dewan, Rumpa Saha, Praveen Kumar Singh, Sajad Ahmad Dar
{"title":"Respiratory Viral Infections in Febrile Children With Lymphoreticular Malignancies: A Single-Centre Descriptive Study","authors":"Keerthana M R, Shukla Das, Charu Jain, Pooja Dewan, Rumpa Saha, Praveen Kumar Singh, Sajad Ahmad Dar","doi":"10.1002/jmv.71180","DOIUrl":"https://doi.org/10.1002/jmv.71180","url":null,"abstract":"<div>\u0000 \u0000 <p>Children with lymphoreticular malignancies are highly vulnerable to respiratory viral infections (RVIs) because of disease- and chemotherapy-related immunosuppression, yet data on their epidemiology, clinical spectrum, and outcomes from resource-limited settings remain scarce. This study aimed to characterize the seasonal distribution, clinical presentation, and outcomes of RVIs other than SARS-CoV-2 in febrile children with lymphoreticular malignancies at a tertiary care centre in India. In this prospective, descriptive, cross-sectional study (May 2023–November 2024), 33 children under 12 years of age with lymphoreticular malignancies were enrolled at a tertiary care centre in Delhi, India, contributing 70 febrile episodes with respiratory symptoms. All episodes were screened for SARS-CoV-2 by rapid antigen test at admission, independent of the viral PCR panel, and none tested positive. Nasopharyngeal swabs were analyzed by multiplex real-time PCR (TRUPCR® Respiratory Viral Pathogen Panel Kit, 3B BlackBio, Bhopal, India; CFX96™, Bio-Rad, Hercules, CA, USA) targeting 18 other respiratory viral pathogens. Respiratory viruses were detected in 34% of episodes (24/70). The most prevalent viruses identified were human coronavirus (HCoV α/β, 21%), human rhinovirus (HRV, 17%), human parainfluenza virus type 3 (HPIV-3, 13%), influenza A (IAV,13%), and human adenovirus (HAdV, 13%). Co-infections occurred in 13% of virus-positive episodes, with HAdV being the predominant co-pathogen. Upper respiratory tract infections (URTI) predominated (87%). Among virus-positive episodes, breathlessness (<i>p</i> = 0.005), URTI/LRTI classification (<i>p</i> < 0.001), erythrocyte sedimentation rate (ESR; <i>p</i> < 0.001), and abnormal chest radiography (<i>p</i> < 0.001) were significantly associated with viral status. Two patients (6%) died, both attributed to lower respiratory tract infection (LRTI) caused by human parainfluenza virus type 4 (HPIV-4). The remaining 66% of episodes were PCR-negative. No SARS-CoV-2 was detected in this cohort at any point during the study period. In approximately one-third of febrile episodes of children with hematologic malignancies, a viral pathogen could be detected. Both fatalities in this cohort were associated with HPIV-4-related LRTI; although the numbers are small, this finding warrants clinical attention and continued epidemiological surveillance in this population. Multiplex PCR supports targeted management; prospective, multicentre stewardship studies are needed.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206020","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}
Shui-Shan Lee, Denise Pui-Chung Chan, Bonnie Chun-Kwan Wong, Danny King Fai Cheung, Ngai Sze Wong
{"title":"Resurgence of Sexually Transmitted Hepatitis C Virus Infection in Men Who Have Sex With Men Living With HIV","authors":"Shui-Shan Lee, Denise Pui-Chung Chan, Bonnie Chun-Kwan Wong, Danny King Fai Cheung, Ngai Sze Wong","doi":"10.1002/jmv.71185","DOIUrl":"https://doi.org/10.1002/jmv.71185","url":null,"abstract":"<p>In 2023–2025, HCV transmission in men who have sex with men (MSM) living with HIV in Hong Kong resurged. This study aims to assess the epidemiologic patterns between 2011 and 2025. Among 288 MSM with sexually acquired HCV infection, 73% were diagnosed at least 12 months after HIV diagnosis, and 98% had ever achieved HIV viral load suppression. Comparing with Period 1 (2015–2022) featuring a large HCV genotype 3a cluster (89 diagnoses) and a few smaller HCV genotype 1a clusters (size of 2 to 13), Period 2 (2023–2025) was dominated by two HCV genotype 1a clusters (7 and 16 new diagnoses). Transmission of genotype 3a viruses subsided in Period 2, with only 3 new diagnoses. Comparing with Period 1, a higher proportion of MSM with HCV diagnoses in Period 2 self-reported sexualised injecting drug use (OR = 3.82, 95% CI 1.59–9.20) and HCV direct-acting antivirals therapy (no treatment as reference group, OR = 3.72, 95%CI 1.82–7.60). The epidemic rebound by a different HCV genotype was likely contributed by increased engagement in chemsex and post-COVID-19 population mobility.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.71185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206026","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}
Alessandra Pavan Lamarca, Melise Chaves Silveira, Renata Campos Azevedo, Maria Angélica Arpon Marandino Guimarães, Claudia Maria Braga de Mello, Adriana Cardoso Camargo, Leandro Magalhães de Souza, Alexandra Lehmkuhl Gerber, Ana Paula C. Guimarães, Andréa Cony Cavalcanti, Ana Tereza Ribeiro Vasconcelos
{"title":"First Phylodynamic Analysis of HRSV-A and HRSV-B in Rio de Janeiro, Brazil, Reveals Recurrent Dispersals From the Megalopolis Center to Suburban Cities","authors":"Alessandra Pavan Lamarca, Melise Chaves Silveira, Renata Campos Azevedo, Maria Angélica Arpon Marandino Guimarães, Claudia Maria Braga de Mello, Adriana Cardoso Camargo, Leandro Magalhães de Souza, Alexandra Lehmkuhl Gerber, Ana Paula C. Guimarães, Andréa Cony Cavalcanti, Ana Tereza Ribeiro Vasconcelos","doi":"10.1002/jmv.71177","DOIUrl":"10.1002/jmv.71177","url":null,"abstract":"<p>Human respiratory syncytial virus (HRSV) is the leading cause of acute lower respiratory tract infections in infants and represents a major burden to public health systems worldwide. Despite its epidemiological relevance, genomic surveillance of HRSV in Brazil remains limited. Here, we investigated the genetic diversity and dispersal dynamics of HRSV-A and HRSV-B in the state of Rio de Janeiro, Brazil, during the period immediately preceding the implementation of maternal vaccination and prophylactic monoclonal antibodies. A total of 136 near-complete HRSV genomes were recovered from respiratory samples collected between May 2024 and June 2025 using metagenomic sequencing. Phylogenetic analyses identified 11 HRSV-A and five HRSV-B lineages, with most sequences belonging to the A.D.3 and B.D.E.1 clades. Phylodynamic reconstructions revealed multiple independent introductions into the state, with the city of Rio de Janeiro acting as the primary within-state dispersal hub. Viral dispersal routes originating from the capital also showed greater mean transmission distances than those from other municipalities. Coinfections with additional respiratory viruses were frequently detected, and most HRSV-positive patients were children under 1 year of age. These results demonstrate that HRSV circulation in Rio de Janeiro is shaped by repeated introductions and strong spatial structuring centered around highly connected urban areas. Our findings underscore the importance of continuous genomic surveillance to monitor viral evolution, characterize transmission dynamics, and support science-based public health strategies against HRSV. Establishing robust monitoring systems will be critical to evaluate the impact of newly implemented immunization programs in Brazil.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.71177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194630","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}
Milena Mikluš, Mario Poljak, Jana Mlakar, Andrej Cokan, Maja Pakiž, Jure Knez, Leyla Al-Mahdawi, Luka Roškar, Mario Gorenjak, Anja Oštrbenk, Grega Gimpelj Domjanič, Andraž Dovnik
{"title":"The Role of Methylation Marker FAM19A4/mir124-2 and HPV Genotype in Active Surveillance of Women With Cervical Intraepithelial Neoplasia Grade 2 (CIN2)","authors":"Milena Mikluš, Mario Poljak, Jana Mlakar, Andrej Cokan, Maja Pakiž, Jure Knez, Leyla Al-Mahdawi, Luka Roškar, Mario Gorenjak, Anja Oštrbenk, Grega Gimpelj Domjanič, Andraž Dovnik","doi":"10.1002/jmv.71175","DOIUrl":"10.1002/jmv.71175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>A substantial proportion of cervical intraepithelial neoplasia grade 2 (CIN2) spontaneously regress, supporting the use of active surveillance over immediate treatment. Identification of prognostic factors associated with higher rates of spontaneous regression could enable better selection of patients in whom such approach would be safe. We evaluated the prognostic value of <i>FAM19A4/miR124-2</i> methylation status, HPV genotype, and baseline cytology for predicting spontaneous regression of CIN2. Women aged 18–40 years with CIN2 were prospectively enroled and followed for 2 years. At baseline, HPV genotyping was performed together with <i>FAM19A4/miR124-2</i> methylation analysis. Among 119 enroled patients, the rate of spontaneous regression of CIN2 was 61.3% (73/119). Regression of CIN2 was significantly associated with HPV genotype (<i>χ</i><sup>2</sup> = 19.374; <i>p</i> = 0.002) and negative methylation result (<i>χ</i><sup>2</sup> = 10.945; <i>p</i> = 0.012). Negative methylation in combination with low-grade cytology and non-HPV16 genotype was associated with regression rates of 71.4% and 70.4%, respectively. Spontaneous regression of CIN2 is more frequent in women with non-HPV16 infection and negative <i>FAM19A4/miR124-2</i> methylation. A combination of these markers improves identification of women with lower risk of disease progression and supports safer implementation of active surveillance and conservative management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>The study was registered at ClinicalTrials.gov as NCT05624827.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182662","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}