Journal of Medical Virology最新文献

{"title":"Lycorine Inhibits Chandipura Virus Replication In Vitro","authors":"Tanvi Agrawal,&nbsp;Shikha Singh,&nbsp;Gurleen Kaur,&nbsp;Shiva Rathore,&nbsp;Harshita Sharma,&nbsp;Gunjan Rajput,&nbsp;Sweety Samal,&nbsp;Amit Awasthi","doi":"10.1002/jmv.70636","DOIUrl":"https://doi.org/10.1002/jmv.70636","url":null,"abstract":"<div>\u0000 \u0000 <p>Chandipura virus (CHPV), a neurotropic member of the Rhabdoviridae family, causes severe paediatric encephalitis outbreaks in India with high fatality rates and no approved antiviral therapies. In this study, lycorine, a plant-derived alkaloid with established broad-spectrum antiviral activity, was evaluated for its efficacy against CHPV. In vitro treatment with lycorine resulted in a &gt; 2.5 log₁₀ reduction in viral, with minimal cytotoxicity and favourable selectivity indices across multiple cell lines. Time-of-addition assays demonstrated that lycorine exerts its antiviral effect during early stages of infection, without affecting the viral entry or egress. Quantitative RT-PCR revealed a significant inhibition of CHPV positive-strand RNA synthesis, indicating disruption of early replication steps. To elucidate the mechanism of action, molecular docking studies were performed using a structural model of CHPV L protein, based on high-homology alignment with Vesicular Stomatitis Virus (VSV) polymerase. Docking and free energy calculations identified two high-affinity lycorine-binding sites within the RdRp catalytic domain, stabilized by hydrogen bonding and aromatic interactions. These findings suggest that lycorine may inhibit CHPV replication by targeting the viral RNA-dependent RNA polymerase. Overall, this study highlights lycorine as a promising antiviral candidate against CHPV and potentially other neurotropic RNA viruses.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223899","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":"Novel Mechanism of the L-Type Voltage-Gated Channels/Calpains Axis in Influenza A Virus-Induced Autophagosome Activity","authors":"Hannah Murphy,&nbsp;Hinh Ly","doi":"10.1002/jmv.70631","DOIUrl":"https://doi.org/10.1002/jmv.70631","url":null,"abstract":"&lt;p&gt;Seasonal influenza viruses can cause up to 1 billion human infections and can result in 290 000–650 000 deaths annually worldwide [&lt;span&gt;1&lt;/span&gt;]. The global influenza burden varies widely due to a complex interplay of factors, such as viral strain characteristics (i.e., transmissibility, severity, and antigenic drift), seasonal patterns (i.e., temperature, humidity, and human behavior), vaccine effectiveness, and immunization coverage [&lt;span&gt;2, 3&lt;/span&gt;]. While vaccines are the most effective means for preventing seasonal influenza A virus (IAV) infections in healthy adults, they provide suboptimal protection for high-risk groups and can be ineffective when antigenic predictions in seasonal vaccine formulation happen to be mismatched with the circulating or emerging virus strains [&lt;span&gt;4&lt;/span&gt;]. In addition to vaccines, antivirals are widely used to control IAV infections, with the main antiviral classes targeting the viral neuraminidase and cap-dependent endonuclease, whereas the M2 inhibitors not being recommended due to the rapid emergent of viral resistance [&lt;span&gt;5, 6&lt;/span&gt;]. The circulating IAV strains continuously develop resistance to all available forms of antivirals that highlight the need for new approaches against IAV infection.&lt;/p&gt;&lt;p&gt;The recently published article by Tian et al., entitled “Influenza A Virus Induces Autophagosome by Inhibiting LTCC/Calpain 2/LC3A Signaling to Promote Viral Replication” in the Journal of Medical Virology [&lt;span&gt;7&lt;/span&gt;], investigated a novel mechanism of the &lt;span&gt;l&lt;/span&gt;-type voltage-gated channels (LTCC)/calpains axis in IAV-induced autophagosome activity. Using the PR8 (H1N1) IAV isolate, the authors demonstrated, through a series of well-thought-out experiments, that IAV infection reduces LTCC-mediated Ca&lt;sup&gt;2+&lt;/sup&gt; influx; in human lung adenocarcinoma A549 cells, Cav1.3 is the predominant LTCC isoform, and its knockdown (KD) phenocopies LTCC blockade, consistent with suppression of Cav1.3 activity during IAV infection.&lt;/p&gt;&lt;p&gt;Briefly summarized, the authors demonstrated that under normal conditions (Figure 1, left), Cav1.3 induces Ca&lt;sup&gt;2+&lt;/sup&gt; influx, activating calpain-2, which cleaves LC3A and maintains normal levels of autophagosomes. However, in PR8 (H1N1) IAV-infected cells (right), Cav1.3 is suppressed, which decreases the Ca&lt;sup&gt;2+&lt;/sup&gt; influx, leading to calpain-2 being inactivated. LC3A is therefore being left uncleaved, and autophagosome accumulation occurs concurrently with IAV blocking the fusion of autophagosomes and lysosomes into autolysosomes. The authors showed that the accumulation of autophagosomes could promote IAV viral replication in human lung adenocarcinoma A549 cells. Under physiological conditions, LC3A is primed at the C-terminus by ATG4 proteases for subsequent lipidation [&lt;span&gt;6&lt;/span&gt;]. This study [&lt;span&gt;7&lt;/span&gt;] extended those findings by showing that calpain-2 can cleave LC3A (aa112-118) to suppress autophagosome formation. The authors also showed t","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224334","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":"Lycorine Inhibits Chandipura Virus Replication In Vitro","authors":"Tanvi Agrawal,&nbsp;Shikha Singh,&nbsp;Gurleen Kaur,&nbsp;Shiva Rathore,&nbsp;Harshita Sharma,&nbsp;Gunjan Rajput,&nbsp;Sweety Samal,&nbsp;Amit Awasthi","doi":"10.1002/jmv.70636","DOIUrl":"https://doi.org/10.1002/jmv.70636","url":null,"abstract":"<div>\u0000 \u0000 <p>Chandipura virus (CHPV), a neurotropic member of the Rhabdoviridae family, causes severe paediatric encephalitis outbreaks in India with high fatality rates and no approved antiviral therapies. In this study, lycorine, a plant-derived alkaloid with established broad-spectrum antiviral activity, was evaluated for its efficacy against CHPV. In vitro treatment with lycorine resulted in a &gt; 2.5 log₁₀ reduction in viral, with minimal cytotoxicity and favourable selectivity indices across multiple cell lines. Time-of-addition assays demonstrated that lycorine exerts its antiviral effect during early stages of infection, without affecting the viral entry or egress. Quantitative RT-PCR revealed a significant inhibition of CHPV positive-strand RNA synthesis, indicating disruption of early replication steps. To elucidate the mechanism of action, molecular docking studies were performed using a structural model of CHPV L protein, based on high-homology alignment with Vesicular Stomatitis Virus (VSV) polymerase. Docking and free energy calculations identified two high-affinity lycorine-binding sites within the RdRp catalytic domain, stabilized by hydrogen bonding and aromatic interactions. These findings suggest that lycorine may inhibit CHPV replication by targeting the viral RNA-dependent RNA polymerase. Overall, this study highlights lycorine as a promising antiviral candidate against CHPV and potentially other neurotropic RNA viruses.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224333","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":"Novel Mechanism of the L-Type Voltage-Gated Channels/Calpains Axis in Influenza A Virus-Induced Autophagosome Activity","authors":"Hannah Murphy,&nbsp;Hinh Ly","doi":"10.1002/jmv.70631","DOIUrl":"https://doi.org/10.1002/jmv.70631","url":null,"abstract":"&lt;p&gt;Seasonal influenza viruses can cause up to 1 billion human infections and can result in 290 000–650 000 deaths annually worldwide [&lt;span&gt;1&lt;/span&gt;]. The global influenza burden varies widely due to a complex interplay of factors, such as viral strain characteristics (i.e., transmissibility, severity, and antigenic drift), seasonal patterns (i.e., temperature, humidity, and human behavior), vaccine effectiveness, and immunization coverage [&lt;span&gt;2, 3&lt;/span&gt;]. While vaccines are the most effective means for preventing seasonal influenza A virus (IAV) infections in healthy adults, they provide suboptimal protection for high-risk groups and can be ineffective when antigenic predictions in seasonal vaccine formulation happen to be mismatched with the circulating or emerging virus strains [&lt;span&gt;4&lt;/span&gt;]. In addition to vaccines, antivirals are widely used to control IAV infections, with the main antiviral classes targeting the viral neuraminidase and cap-dependent endonuclease, whereas the M2 inhibitors not being recommended due to the rapid emergent of viral resistance [&lt;span&gt;5, 6&lt;/span&gt;]. The circulating IAV strains continuously develop resistance to all available forms of antivirals that highlight the need for new approaches against IAV infection.&lt;/p&gt;&lt;p&gt;The recently published article by Tian et al., entitled “Influenza A Virus Induces Autophagosome by Inhibiting LTCC/Calpain 2/LC3A Signaling to Promote Viral Replication” in the Journal of Medical Virology [&lt;span&gt;7&lt;/span&gt;], investigated a novel mechanism of the &lt;span&gt;l&lt;/span&gt;-type voltage-gated channels (LTCC)/calpains axis in IAV-induced autophagosome activity. Using the PR8 (H1N1) IAV isolate, the authors demonstrated, through a series of well-thought-out experiments, that IAV infection reduces LTCC-mediated Ca&lt;sup&gt;2+&lt;/sup&gt; influx; in human lung adenocarcinoma A549 cells, Cav1.3 is the predominant LTCC isoform, and its knockdown (KD) phenocopies LTCC blockade, consistent with suppression of Cav1.3 activity during IAV infection.&lt;/p&gt;&lt;p&gt;Briefly summarized, the authors demonstrated that under normal conditions (Figure 1, left), Cav1.3 induces Ca&lt;sup&gt;2+&lt;/sup&gt; influx, activating calpain-2, which cleaves LC3A and maintains normal levels of autophagosomes. However, in PR8 (H1N1) IAV-infected cells (right), Cav1.3 is suppressed, which decreases the Ca&lt;sup&gt;2+&lt;/sup&gt; influx, leading to calpain-2 being inactivated. LC3A is therefore being left uncleaved, and autophagosome accumulation occurs concurrently with IAV blocking the fusion of autophagosomes and lysosomes into autolysosomes. The authors showed that the accumulation of autophagosomes could promote IAV viral replication in human lung adenocarcinoma A549 cells. Under physiological conditions, LC3A is primed at the C-terminus by ATG4 proteases for subsequent lipidation [&lt;span&gt;6&lt;/span&gt;]. This study [&lt;span&gt;7&lt;/span&gt;] extended those findings by showing that calpain-2 can cleave LC3A (aa112-118) to suppress autophagosome formation. The authors also showed t","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223898","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":"Accurate and Cost-Efficient Whole Genome Sequencing of Hepatitis B Virus Using Nanopore","authors":"Joakim B. Stenbäck,&nbsp;Daniel Schmidt,&nbsp;Ulrika Noborg,&nbsp;Joel Gustafsson,&nbsp;Peter Norberg,&nbsp;Maria E. Andersson,&nbsp;Michael X Fu,&nbsp;Heli Harvala,&nbsp;Johan Ringlander","doi":"10.1002/jmv.70630","DOIUrl":"https://doi.org/10.1002/jmv.70630","url":null,"abstract":"<p>Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this study was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole relaxed circular HBV genome found in circulating viral particles and covalently closed circular DNA in infected hepatocytes, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing, and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log₁₀ IU/mL with MagNA pure 96 extraction and &lt; 2 log₁₀ IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62−3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging from 6 to 37 euros. We conclude that whole genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis, and genotyping of HBV in a routine laboratory setting.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223900","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":"Accurate and Cost-Efficient Whole Genome Sequencing of Hepatitis B Virus Using Nanopore","authors":"Joakim B. Stenbäck,&nbsp;Daniel Schmidt,&nbsp;Ulrika Noborg,&nbsp;Joel Gustafsson,&nbsp;Peter Norberg,&nbsp;Maria E. Andersson,&nbsp;Michael X Fu,&nbsp;Heli Harvala,&nbsp;Johan Ringlander","doi":"10.1002/jmv.70630","DOIUrl":"https://doi.org/10.1002/jmv.70630","url":null,"abstract":"<p>Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this study was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole relaxed circular HBV genome found in circulating viral particles and covalently closed circular DNA in infected hepatocytes, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing, and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log₁₀ IU/mL with MagNA pure 96 extraction and &lt; 2 log₁₀ IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62−3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging from 6 to 37 euros. We conclude that whole genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis, and genotyping of HBV in a routine laboratory setting.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224226","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":"Interferon Gamma Injection and Its Effect on the Respiratory Anelloviridae Population in ICU Ventilated Patients","authors":"Simon Bulteau,&nbsp;Martin Braud,&nbsp;Mélanie Petrier,&nbsp;Louise Castain,&nbsp;Hussein Anani,&nbsp;Cécile Peltier,&nbsp;Lenha Mobuchon,&nbsp;Marwan Bouras,&nbsp;Delphine Flattres,&nbsp;Jeremie Poschmann,&nbsp;Laurence Josset,&nbsp;Antoine Roquilly,&nbsp;Céline Bressollette-Bodin","doi":"10.1002/jmv.70612","DOIUrl":"10.1002/jmv.70612","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune dysfunctions induced by critical illness are associated with an increased risk of hospital-acquired pneumonia (HAP) in intensive care unit (ICU) patients. The use of immunomodulatory molecules in this setting is under evaluation. The presence of persistent viruses, such as anelloviruses (AVs) or herpesviruses, which are frequently detected in respiratory samples, may indicate immune dysfunction. Herpesvirus infections are associated with increased morbidity in ICU patients, and variations in AV DNA loads are associated with rejection events in immunocompromised patients. We investigated the respiratory viral landscape of 94 patients during the first week under invasive mechanical ventilation using quantitative PCR and targeted metagenomics after capture probe enrichment. The patients were included in a placebo-controlled randomized clinical trial testing IFNγ for the prevention of HAP. We measured AV and herpes simplex virus-1 (HSV-1) DNA loads over time in respiratory samples collected at admission (<i>n</i> = 54), and on Days 3 (<i>n</i> = 73) and 7 (<i>n</i> = 57) after admission. There were no significant differences in mortality, HAP, the development of acute respiratory distress syndrome (ARDS), HSV, or AV DNA detection between patients treated with IFNg and those who received a placebo. Patients who developed HAP had a significantly higher AV DNA load in tracheal aspirates over time (<i>p</i> = 0.011) than those who did not. Target enrichment analysis revealed AV presence in all respiratory samples, with no differences observed in AV composition between IFNg-treated and placebo patients, or between HAP and noHAP patients.</p>\u0000 <p><b>Trial Registration:</b> CPP Ouest II 17/02/2021 (avis N°2021/03); ClinicalTrial.gov number: NCT04793568.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206323","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":"Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients","authors":"Alain R. Thierry,&nbsp;Tom Usher,&nbsp;Cynthia Sanchez,&nbsp;Simone Turner,&nbsp;Chantelle Venter,&nbsp;Brice Pastor,&nbsp;Maxine Waters,&nbsp;Anel Thompson,&nbsp;Alexia Mirandola,&nbsp;Ekaterina Pisareva,&nbsp;Corinne Prevostel,&nbsp;Gert J. Laubscher,&nbsp;Douglas B. Kell,&nbsp;Etheresia Pretorius","doi":"10.1002/jmv.70613","DOIUrl":"10.1002/jmv.70613","url":null,"abstract":"<p>The persistence of vasculo-thrombotic complications has been put forward as a possible contributing factor in the Long COVID (LC) syndrome. Given the recently reported separate demonstration of the association of LC with elevated levels of heterogenous fibrin(ogen) amyloidogenic particles (microclots) and with those neutrophil extracellular traps (NETs), markers that are linked to thromboinflammation, this study considers the association of microclots with NETs. The results show that NETs markers (Myeloperoxydase, Neutrophil Elastase, and circulating DNA) are quantitatively and structurally associated with the size and number of microclots in patients with LC. These markers showed a strong diagnostic performance, both independently and when combined. Our study revealed that NETs may be a component of circulating microclots. We suggest that higher NETs formation might promote the stabilization of microclots in the circulation, potentially leading to deleterious effects which contribute causally to the LC syndrome.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206326","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":"RSV-Induced Glutaric Acid Modulates Neuronal Mitochondrial Heterogeneity via the Lung−Brain Axis","authors":"Taorui Du,&nbsp;Ousman Bajinka,&nbsp;Amie N. Joof,&nbsp;Yurong Tan,&nbsp;Ling Chu","doi":"10.1002/jmv.70625","DOIUrl":"10.1002/jmv.70625","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>The study was designed to explore how glutaric acid induced by respiratory syncytial virus (RSV) infection affects nerve cell mitochondrial heteroplasmy. An RSV infection animal model was established, and lung tissues were collected after 7 days for metabolomic analysis. Then, a neuroinflammatory cell model was constructed with lipopolysaccharide (LPS). The CCK8 assay detected proliferation, the DCFH-DA probe assessed reactive oxygen species (ROS) levels, and ELISA measured IL-1, IL-4, IL-6, and IFN-γ levels in HT-22 cells. RT-qPCR detected Drp1 and Mfn2 expression levels to study the mechanism of glutaric acid-exacerbated neuroinflammation. Immunofluorescence and RT-qPCR detected the effects of glutaric acid on neuron biomarkers in the lung (PGP9.5) and brain (NeuN). Bioinformatics screened glutaric acid-interacting proteins, and the enzymatic activities of NAD-dependent malate dehydrogenase (NAD-ME) were validated at cellular and animal levels. High-performance liquid chromatography (HPLC) detected glutaric acid content in blood and brain tissues. After glutaric acid treatment, Drp1 protein expression increased, Mfn2 decreased, and ROS, IL-1, and IL-6 cytokine levels rose significantly. Glutaric acid affects the central nervous system by disrupting the lung neural network, causing mitochondrial homeostasis dysregulation. Its interaction with NAD-ME accelerates mitochondrial imbalance. Glutaric acid induced by RSV infection aggravates neuroinflammation by affecting nerve cell mitochondrial homeostasis via the lung−brain axis. These findings offer new insights into RSV-induced neuroinflammation and potential targets for neuroprotective strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199678","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":"Mitochondrial Disruption in Viral-Mediated Neuronal Injury: A Mechanistic Perspective","authors":"Shuqi Shi,&nbsp;Mingzhu Zhai,&nbsp;Benqing Wu,&nbsp;Wuping Sun","doi":"10.1002/jmv.70626","DOIUrl":"10.1002/jmv.70626","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuronal injury is a major pathological issue that cannot be ignored during viral infections. Mitochondria, the energy factories of the cell, play a unique role in this scenario and are severely impacted when viruses infect host cells. Viruses invade and infect cells via specific mechanisms, causing changes in cellular structure and function. These changes not only directly affect mitochondria but also disrupt their normal function through indirect pathways. This paper reviews the mechanisms of mitochondrial damage induced by infections with SARS-CoV-2, herpesviruses, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), providing new insights and strategies for preventing and treating neuronal injury.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199720","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}