Journal of Medical Virology最新文献

{"title":"Analysis of Variants' Dynamic Using the CLIMB Database in COVID-19 Patients Admitted to Hospitals of Barts Health NHS Trust","authors":"Concetta Piazzese,&nbsp;Sophie Williams,&nbsp;Adam Brentall,&nbsp;Beatrix Kele,&nbsp;Jon Bible,&nbsp;Kathryn Harris,&nbsp;Teresa Cutino-Moguel","doi":"10.1002/jmv.70402","DOIUrl":"https://doi.org/10.1002/jmv.70402","url":null,"abstract":"<p>The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant global health challenges. This study analyzes the dynamics of SARS-CoV-2 variants among patients admitted to Barts Health National Health Service (NHS) Trust hospitals using data from the CLIMB-COVID decentralized digital infrastructure allowing precise identification of SARS-CoV-2 variants. A total of 423 patients admitted between October 2020 and March 2021 were included in the study and divided into two groups: the alpha lineage group, which comprised the B.1.1.7 variant, and the other lineages group, which included all other variants. Whole-genome sequencing of SARS-CoV-2 genomes was conducted using the COVID-CLIMB pipelines. Clinical outcomes, such as mortality rates and deterioration within 28 days, were analyzed. To ensure robust findings, analyzes were adjusted for confounding factors, including age and comorbidities. Our findings revealed a significant increase in mortality with age for the alpha lineage and other lineages. The study underscores the importance of age adjustment in clinical studies to accurately assess the impact of different variants. Consistent genomic sequencing and data completeness are crucial for obtaining reliable results and guiding public health responses. These insights are vital for improving patient outcomes and providing a truthful picture of the pandemic, informing both current and future healthcare strategies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125987","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":"Disruption of ATR Signaling by Epstein–Barr Virus Latent Membrane Protein 1 Sensitizes Nasopharyngeal Carcinoma Cells to Cisplatin","authors":"Gabriella Zarkovic,&nbsp;Phillip Ziegler,&nbsp;Jennifer Hye-Rim Lee,&nbsp;Brooke Dresden,&nbsp;Amit Kumar,&nbsp;Masahiro Shuda,&nbsp;Alan Bäckerholm,&nbsp;Kathy Ho Yen Shair","doi":"10.1002/jmv.70407","DOIUrl":"https://doi.org/10.1002/jmv.70407","url":null,"abstract":"<p>Nasopharyngeal carcinoma (NPC) occurs with high incidence in Southeast Asia where almost all tumors are associated with Epstein–Barr virus (EBV) infection. Cisplatin is used in combination chemotherapy. In this study, we determined that the EBV oncoprotein, latent membrane protein 1 (LMP1), perturbs DNA damage response (DDR) signaling, activation of cell cycle checkpoints, and sensitivity to cisplatin in NPC cells (HK1). Hypersensitivity was validated by LMP1 knockdown and CRISPR/Cas9 targeting in HK1-EBV cells with latent EBV infection. The conserved PxQxT motif (in CTAR1) and Y384 residue (in CTAR2) were required for the hypersensitivity. Inhibition of ATR (VE821 or AZD6738), but not ATM (KU55933 or AZD0156), phenocopied the G1 arrest and hypersensitivity. Attenuation of DDR signaling and hypersensitivity by LMP1 or ATR inhibition was also observed in the C17 NPC cell line with restored stable LMP1 expression. LMP1 expression in NPC tumors is highly variable. Publicly available RNA-sequencing data from microdissected NPC tumors showed that LMP1 expression in the primary tumors was the lowest in cisplatin-treated patients that experienced recurrence. These findings could have clinical significance in stratifying NPC patients such that tumors with limited or variable LMP1 expression might benefit from ATR inhibitor therapy.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118067","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":"Environmental Surveillance of Hepatitis E Virus and Rat Hepatitis E Virus in Portugal and Spain, 2020–2022","authors":"Sérgio Santos-Silva,&nbsp;Marta Lois,&nbsp;Ana Machado,&nbsp;Adriano Bordalo,&nbsp;Andreia V. S. Cruz,&nbsp;Helena M. R. Gonçalves,&nbsp;Wim H. M. Van der Poel,&nbsp;Maria S. J. Nascimento,&nbsp;António Rivero-Juarez,&nbsp;Jesús L. Romalde,&nbsp;João R. Mesquita","doi":"10.1002/jmv.70414","DOIUrl":"https://doi.org/10.1002/jmv.70414","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis E virus (<i>Paslahepevirus balayani</i> [HEV]) is an important cause of acute viral hepatitis globally, with zoonotic genotypes linked to transmission through consumption of raw or undercooked swine meat or products. Recently, <i>Rocahepevirus ratti</i> (RHEV), member of <i>Hepeviridae</i> family, has emerged as a potential public health concern, with some human cases being reported. The present study aimed to investigate the presence of HEV, as well as RHEV in wastewaters from northern Portugal and Spain (nPS). Given the reported decline in HEV detection in swine from several regions of the world, we also aimed to explore HEV and RHEV in fattened swine fecal samples from the same region of the wastewaters. Between April 2020 and January 2022, a total of 44 wastewater samples were collected from wastewater treatment plants in nPS, alongside 400 fattened swine fecal samples from five farms of the same regions. Wastewater and swine fecal samples RNA extracts were screened for HEV using pangenotypic RT-qPCR and for RHEV using a RT-qPCR assay followed by characterization using nested RT-PCR. Regarding wastewaters, three tested positive for HEV, while 39 out of 44 tested positive for RHEV. Wastewater analysis in the Iberian Peninsula revealed a predominance of RHEV and a near absence of HEV. The absence of both viruses was observed in the swine fecal samples. This combined analysis showing near/total absence of HEV in wastewaters/fattened swine samples warrants further studies. High levels of RHEV in wastewater might also pose environmental transmission risks, particularly for individuals with occupational exposure, emphasizing the need for enhanced zoonotic virus surveillance in urban areas.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118068","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":"DNAJC9 Binds to and Enhances the Transcription of Hepatitis B Virus cccDNA by Recruiting Histone H3.3","authors":"Tianhao Mao,&nbsp;Xinyu Du,&nbsp;Yukun Li,&nbsp;Zhao Zhou,&nbsp;Deyao Li,&nbsp;Liwei Zheng,&nbsp;Ting Zhang,&nbsp;Guixin Li,&nbsp;Danli Yang,&nbsp;Xiangmei Chen,&nbsp;Fengmin Lu","doi":"10.1002/jmv.70390","DOIUrl":"https://doi.org/10.1002/jmv.70390","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the transcriptional template in HBV replication, is transcriptionally regulated by multiple host proteins such as epigenetic factors and transcription factors. This study aims to identify novel host proteins interacting with cccDNA and regulating its activity in HBV replication. Mass spectrometry analysis identified 129 host proteins associated with biotinylated cccDNA surrogate HBVcircle. A siRNA library screening demonstrated that knockdown of DNAJC9, CEBPZ, and EIF3A in HepG2 cells transfected with HBVcircle reduced the levels of HBsAg and HBeAg in the supernatant. Knockdown of DNAJC9 in HBV replication and infection cell models restricted viral replication, while the DNAJC9 overexpression showed an opposite trend. DNA pull-down, cccDNA ChIP, and immunofluorescence experiments indicated that DNAJC9 can bind to cccDNA in a manner independent of histones and specific DNA sequences. Dual luciferase reporter assay demonstrated that knockdown of DNAJC9 reduces the transcriptional activity of HBV promoters and enhancers. Co-IP and cccDNA ChIP experiments showed that DNAJC9 can interact with histone H3.3, and knockdown of DNAJC9 reduced H3.3, H3K4me3, and H3K27ac on cccDNA. In the HepAD38 or HepG2-NTCP cells, HBV replication led to a decrease in the cytoplasmic distribution and an increase in the nuclear distribution of DNAJC9. Histone chaperone DNAJC9 can bind to cccDNA in a histone-independent manner. DNAJC9 upregulates cccDNA transcription and viral replication by increasing the density of H3.3, H3K4me3, and H3K27ac on cccDNA, thereby activating its promoters and enhancers. HBV replication may promote the nuclear localization of DNAJC9 protein, thus facilitating active transcription and replication of HBV.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118066","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":"Clinical and Epidemiological Insights into a Parainfluenza Virus Type 3 Outbreak in Multiple Myeloma Patients","authors":"Sarah Timsit,&nbsp;Guillaume Mellon,&nbsp;Nathalie Forgeard,&nbsp;Séverine Mercier-Delarue,&nbsp;Nadia Mahjoub,&nbsp;Victor Euzen,&nbsp;Stéphanie Harel,&nbsp;Dikelele Elessa,&nbsp;Nathalie Osinski,&nbsp;Elise Diaz,&nbsp;Bruno Royer,&nbsp;Bertrand Arnulf,&nbsp;Maud Salmona,&nbsp;Jérôme Legoff","doi":"10.1002/jmv.70411","DOIUrl":"https://doi.org/10.1002/jmv.70411","url":null,"abstract":"<p>Human parainfluenza virus type 3 (HPIV-3) can be responsible for mild to severe respiratory infections and hospital epidemics. We investigated an outbreak in a hematology unit. Respiratory viruses were screened using multiplex PCR. HPIV-3 quantification and whole-genome sequencing were performed on HPIV-3 positive respiratory samples. Clinical characteristics, infection progression, incidence rates of respiratory viruses within the hospital and detection of respiratory viruses were documented, along with the reinforcement of infection prevention and control (IPC) measures implemented. Between November 2022, and January 2023, HPIV-3 was identified in 20 of 113 hematology patients (17.7%), of whom 80% had multiple myeloma. A majority of HPIV-3-positive patients developed pneumonia (60%), and mortality was notably higher (35%) compared to patients who were negative (3%, <i>p</i> &lt; 0.0001). Respiratory HPIV-3 viral loads were similar between patients with and without pneumonia. In parallel, HPIV-3 incidence in the hospital overall was lower than in the hematology unit (<i>p</i> &lt; 0.0001). Air virus screening showed the detection of HPIV-3 in the air in different areas, and whole-genome sequencing confirmed the circulation of a single HPIV-3 strain. Strengthened IPC measures were associated with the containment of the outbreak. HPIV-3 has high epidemic potential in patients with multiple myeloma and causes severe infections. Our findings highlight the need for routine HPIV-3 testing in hematology units.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108899","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":"High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay","authors":"Shuai Zhen","doi":"10.1002/jmv.70415","DOIUrl":"https://doi.org/10.1002/jmv.70415","url":null,"abstract":"<div>\u0000 \u0000 <p>Human papillomavirus (HPV) related cancers often arise from a background of chronic inflammation. Systemic treatment for advanced HPV-related cancers has been disappointing due to their strong resistance to chemotherapy and even to tyrosine kinase inhibitors (TKIs). Recently, the use of immune checkpoint inhibitor (ICI) therapy has revolutionized the systemic treatment of advanced HPV-related cancers. For the first time, clinical trials testing ICIs, anti-CTLA-4, and anti-PD1/PDL1 reported a survival benefit in patients with sorafenib resistance. However, it took a long time to find the right combination regimen to use ICIs in combination with the antiangiogenic agent bevacizumab to substantially prolong overall survival (OS) of patients with advanced HPV-related cancer after sorafenib. This review provides a comprehensive history of ICI therapy in HPV-related cancer, up-to-date information on the latest ICI clinical trials, and discusses the recent development of novel ICIs that would potentially lead to a new checkpoint blockade therapy for advanced HPV-related cancer.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108885","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":"Postacute Sequelae of COVID-19 Across 12 Major Health Domains and 141 Diseases in Individuals With Mental Illness Among COVID-19 Survivors: A Population-Based Cohort Study in South Korea","authors":"Jiseung Kang,&nbsp;Jaeyu Park,&nbsp;Yejun Son,&nbsp;Hyeon Jin Kim,&nbsp;Guillaume Fond,&nbsp;Laurent Boyer,&nbsp;Masoud Rahmati,&nbsp;Hayeon Lee,&nbsp;Dong Keon Yon","doi":"10.1002/jmv.70406","DOIUrl":"https://doi.org/10.1002/jmv.70406","url":null,"abstract":"<div>\u0000 \u0000 <p>Understanding whether individuals with mental illness, who face challenges related to healthcare barriers, are more vulnerable to postacute sequelae of COVID-19 is limited. Here, we investigated the potential association between pre-existing mental illness and postacute sequelae of COVID-19 across 12 major health domains and 141 specific diseases in COVID-19 survivors. The large-scale, population-based cohorts from South Korea (K-COV-N cohort) used in the study included 8 632 221 individuals aged 20 years or older who were infected with SARS-CoV-2 between January 1, 2020, and December 31, 2022. The risk of postacute sequelae of COVID-19 was assessed in the 1:2 propensity score-matched cohorts, comprising 12 major health domains and 141 diseases based on the ICD-10 code, following mental illness among patients with COVID-19. We assessed the time attenuation effect of major health outcomes after 30 days following SARS-CoV-2 infection. Multiple subgroup analyses were conducted by severity of mental illness, COVID-19 severity, vaccination, and SARS-CoV-2 strain. After 1:2 exposure-driven propensity score matching, we identified 1 341 320 participants with mental illness (mean age, 49.51 [SD, 13.82] years; 62.27% female) and 2 653 597 controls (mean age, 48.78 [SD, 13.75] years; 62.03% female). Individuals with mental illness exhibited significantly higher risks across all 12 major health domains, including: infectious and parasitic events (adjusted hazard ratio [aHR], 1.36 [95% CI, 1.33–1.38]), blood and immune-related events (1.21 [1.17–1.26]), endocrine, nutritional, and metabolic events (1.21 [1.18–1.24]), nerve-related events (2.13 [2.07–2.19]), eye-related events (1.29 [1.25–1.34]), ear and mastoid events (1.52 [1.50–1.54]), circulatory events (1.25 [1.17–1.35]), respiratory events (1.26 [1.24–1.29]), digestive events (1.41 [1.40–1.41]), skin-related events (1.34 [1.30–1.38]), musculoskeletal events (1.42 [1.41–1.43]), and genitourinary events (1.54 [1.18–2.01]). Of the 141 postacute sequelae of COVID-19, 133 showed significantly increased risks. The association was strongest within the first 6–12 months after SARS-CoV-2 infection, with risks progressively attenuating beyond 12 months and nearly disappearing after 18 months. Subgroup analysis revealed that individuals with mild mental illness exhibited higher aHRs for 11 of the 12 health outcome domains compared with those with severe mental illness. Altogether, our findings show the increased risk of postacute sequelae of COVID-19 across 12 major health domains in individuals with mental illness among COVID-19 survivors. These findings highlight the need for targeted monitoring and intervention strategies to address the vulnerabilities of this population, particularly during the post-COVID-19 period.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108913","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":"Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1)","authors":"Edward N. Janoff,&nbsp;Mei-Chiung Shih,&nbsp;Curtis Donskey,&nbsp;Ilana Belitskaya-Levy,&nbsp;Norbert Brau,&nbsp;Maria C. Rodriguez-Barradas,&nbsp;Ernest Chan,&nbsp;Peter Zimmerman,&nbsp;Elliott K. Miller,&nbsp;Leroy B. Vaughan,&nbsp;J. Daniel Markley,&nbsp;Alexa M. Goldberg,&nbsp;Peruvemba Sriram,&nbsp;Antonio Anzueto,&nbsp;Lauren Uyeda,&nbsp;Lisa Zehm,&nbsp;Ashlea Wills,&nbsp;Caitlin Hutchinson,&nbsp;Lucas Jones,&nbsp;Dianne Peterson,&nbsp;Robert J. Ringer,&nbsp;Larry Dumont,&nbsp;Theresa Gleason,&nbsp;Robert A. Bonomo,&nbsp;Jeffrey L. Curtis,&nbsp;Sheldon T. Brown,&nbsp;the CURES-1 Trials Consortium","doi":"10.1002/jmv.70349","DOIUrl":"https://doi.org/10.1002/jmv.70349","url":null,"abstract":"<div>\u0000 \u0000 <p>In the initial absence of proven therapies, empirical COVID-19 convalescent plasma (CCP) was rapidly introduced for individuals hospitalized for COVID-19. Seventy-five participants were randomized from November 2020 to June 2021 in a double-blind, multi-site, placebo-controlled, randomized trial (VA CURES-1) evaluating the impact of CCP vs. saline in Veterans hospitalized with COVID-19 with hypoxemia. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 29. We analyzed clinical outcomes, nasal viral RNA, plasma cytokines and viral evolution over time. Among 40 participants receiving saline and 35 receiving CCP with high neutralizing titers (median 1:1420), the percent reaching the primary outcome was similar (10%), as were time to clinical recovery and to nasal viral clearance. By whole genome sequencing, viral molecular complexity evolved pre- to posttreatment more frequently in recipients of saline vs. CCP (4 of 7 (57.1%) vs. 1 of 4 (25%), respectively), based on numbers of mixed allele positions. Numbers of amino acid-changing, non-synonymous mutations in the spike protein were greater in saline vs. CCP recipients. Both outcomes suggested purifying selection (reduced overall viral infection complexity) following CCP. In conclusion, convalescent plasma showed no significant clinical impact but may influence SARS-CoV-2 complexity.</p>\u0000 <p><b>Trial Registration:</b> ClinicalTrials.gov Identifier: NCT04539275</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108737","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":"Unraveling the Role of Mutations Outside the Basal Promoter and Precore Regions in the HBeAg-Negative Stage of Chronic Hepatitis B","authors":"María Mercedes Elizalde,&nbsp;María Cecilia Monzani,&nbsp;Nicolás Octavio Favale,&nbsp;Belén Bouzas,&nbsp;Lilia Mammana,&nbsp;Rodolfo Campos,&nbsp;Diego Flichman","doi":"10.1002/jmv.70398","DOIUrl":"https://doi.org/10.1002/jmv.70398","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis B e antigen (HBeAg) seroconversion is a crucial event in the natural history of chronic hepatitis B virus (HBV) infection, marked by a significant decrease in viral load and the emergence of mutations that suppress HBeAg expression. However, these mutations alone do not fully account for the reduction in viral load. This study investigated the biological features and pathogenic roles of mutations outside the basal core promoter (BCP) and precore regions during the HBeAg-negative stage of chronic infection. Full-length HBV genomes from HBeAg-positive (<i>n</i> = 180) and HBeAg-negative (<i>n</i> = 328) genotype D datasets were analyzed, revealing significantly higher genomic heterogeneity in HBeAg-negative sequences compared with HBeAg-positive genomes (50.4 ± 16.0 vs. 26.6 ± 10.5 nucleotide changes per genome). Twenty-six hotspot amino acid mutations associated with the HBeAg-negative stage were identified, with over half located in the Core region. Subsequently, full-length HBV genomes from six HBeAg-negative patient-derived serum samples were obtained by PCR amplification followed by Sanger sequencing. Infectious clones generated from these genomes, each carrying between 21 and 66 amino acid substitutions, were characterized, showing that mutations in this stage differentially affected viral fitness in vitro by up- or downregulating HBV-DNA levels (ranging from 0.2 to 5 times those of the wild-type isolate), modulating capsid assembly, and altering the expression, secretion, and subcellular localization of viral proteins. In conclusion, while mutations in the BCP and precore regions are the primary drivers of HBeAg seroconversion, mutations outside these regions significantly influence HBV biology and potentially contribute to viral pathogenicity, underscoring the complex interplay between host and virus during the HBeAg-negative stage of chronic infection.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108900","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":"Overexpression of mRNA Leukocyte-Associated Immunoglobulin-Like Receptor 2 (LAIR-2) Levels Correlates With Immune Cell Subtype Infiltration, T Cell Exhaustion, and Its Prognostic Potential in Hepatocellular Carcinoma","authors":"Aya Mohamed Ahmed Ibrahim,&nbsp;Abeer I. Abd El-Fattah,&nbsp;Olfat Gamil Shaker,&nbsp;Ahmed A. Youssef","doi":"10.1002/jmv.70417","DOIUrl":"https://doi.org/10.1002/jmv.70417","url":null,"abstract":"<div>\u0000 \u0000 <p>The immunological microenvironment in hepatocellular carcinoma (HCC) is characterized by impaired immune responses. Significantly, LAIR-2 levels correlate with immune cell subtype infiltration, T cell exhaustion, and its prognostic potential in HCC. This study aims to assess the diagnostic and prognostic significance of expression levels of Pax8-AS1 and LAIR-2 in patients with HCV and their association with susceptibility to HCC. Pax8-AS1 and LAIR-2 expression levels in the serum of patients were analyzed using reverse transcription-quantitative PCR (RT-PCR), while the efficacy of biomarkers in prognostic prediction was assessed by using bioinformatics. The current research showed that Pax8-AS1 had low expression levels in the blood and a positive correlation with portal vein diameter in HCC, which is predictive of portal vein thrombosis (PVT) development. The expression levels of LAIR-2 were elevated in HCV and HCC cases. In HCC, there was an inverse correlation among LAIR-2 and hematology laboratory tests, albumin, tumor nodules, ascites, and splenomegaly. However, there was a positive correlation among LAIR-2, spleen diameter, AFP, and bilirubin. Pax8-AS1 and LAIR-2 showed remarkable diagnostic efficacy, with sensitivity and specificity values, respectively (<i>p</i> &lt; 0.001) (80%, 80% and 90%, 100%) in HCV and (96.7%, 80% and 93%, 100%) in HCC. LAIR-2 overexpression positively correlates with several critical genes associated with exhausted T cells immune infiltration, T cells, CD4+, and CD8+ T cells. The present data support a novel diagnostic and prognostic function for LAIR2 and PAX8-AS1 in HCC, and its significant association with T cell exhaustion contributes to its promotion in HCC. LAIR-2 detection could provide a new prognosis prediction method, and regulation within T-cell exhaustion, optimizing anti-HCC treatments.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 5","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108886","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}