Journal of NeuroVirology最新文献

{"title":"CRISPR-mediated excision of HTLV-1 reduces proviral loads in PBMCs from HAM/TSP patients.","authors":"Samuel Brancazio, Kamel Khalili, Steven Jacobson, Rafal Kaminski","doi":"10.1007/s13365-026-01333-7","DOIUrl":"10.1007/s13365-026-01333-7","url":null,"abstract":"<p><p>CRISPR technology is emerging as a promising therapeutic approach for eliminating chronic viral infections, such as herpesviruses and HIV. Here, for the first time, we demonstrate in vitro that CRISPR can be used to excise the HTLV-1 genome and reduce proviral loads in PBMCs from HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) patients. Single treatment with CRISPR-RNP (ribonucleoprotein) complexes composed of two gRNAs targeting the HTLV-1 env gene and 3'LTR sequences resulted in excision of a 2613 bp segment of the proviral genome, spanning tax and HBZ genes, without detectable off-target activity. Furthermore, CRISPR treatment led to over 50% reduction in proviral loads 5 days post-electroporation. Our data indicate that CRISPR-Cas9 gene editing can be used as a therapeutic strategy to eliminate HTLV-1 DNA from infected cells and may serve as a platform for curing HAM/TSP.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From viral epigenetic reprogramming to neuroinflammation: Mechanisms driving neurodegeneration.","authors":"Chaitali Vora, Vaishali Saini, Maxim Shevtsov, Pankaj Trivedi, Avinash Sonawane, Hem Chandra Jha","doi":"10.1007/s13365-026-01341-7","DOIUrl":"https://doi.org/10.1007/s13365-026-01341-7","url":null,"abstract":"<p><p>Viruses exploit host genetic machinery to establish chronic infections and contribute to chronic neurodegenerative and immune disorders. By manipulating DNA methylation, histone modifications, and non-coding RNA networks, viruses such as Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Zika virus (ZIKV), and Human immunodeficiency virus (HIV) induce epigenetic changes that silence or delay the host antiviral defenses and reprogram host gene expression. For instance, EBV recruits DNA methyltransferases (DNMTs) to hypermethylate genes such as SOCS1 while ZIKV disrupts neuronal DNA methylation via heterochromatinization. Concurrently, HIV-1 encoded Tat protein disrupts H3K27 acetylation in astrocytes that potently triggers glutamate excitotoxicity. Viruses also subvert the chromatin architecture to modulate 3D interactions and reader protein recruitment, thus rewiring transcriptional programs. Such epigenetic alterations correlate with neuropathologies wherein global hypomethylation and histone acetylation contribute to Alzheimer's or Parkinson's disease. Although several mechanisms are known, the field of viral control in neuroepigenetics is underexplored. Emerging therapies that target viral-host epigenetic crosstalk through DNMT or HDAC inhibitors are promising. This review highlights how neurotropic viruses co-opt epigenetic pathways to drive neurodegeneration. We also explore biomarker-driven strategies for personalized interventions in neurodegenerative disorders thus emphasizing potential epigenetic editing tools to restore neuronal homeostasis.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cannabis use on white matter hyperintensities in adults with and without chronic HIV disease.","authors":"Sreelakshmi Shaji, Sheri L Towe, Paul J Laurienti, Robert G Lyday, Jonathan H Burdette, Christina S Meade","doi":"10.1007/s13365-026-01338-2","DOIUrl":"10.1007/s13365-026-01338-2","url":null,"abstract":"<p><p>White matter hyperintensities (WMH) are prevalent among people living with HIV (PLWH), even with sustained viral suppression on antiretroviral therapy. This study investigated whether cannabis use contributes to additional WMH load among PLWH and its association to neurocognitive function. A total of 296 adult participants, stratified by HIV and cannabis status (74 control, 73 cannabis-only, 76 HIV-only and 73 HIV+cannabis) were enrolled. High resolution anatomical MRI and fluid-attenuated inversion recovery (FLAIR) images were collected, along with a battery of neuropsychological tests. Periventricular (pvWMH) and deep (dWMH) WMH loads were quantified using an automated pipeline. Statistical tests were employed to examine the main and interaction effects of HIV and cannabis use on WMH, and to explore the association of WMH loads with neuropsychological performance. The cohort had a mean age of 39.84 years, and all PLWH had sustained viral suppression. pvWMH loads were higher in the cannabis-only and HIV-only groups compared to controls. A significant interaction effect of HIV by cannabis was found for pvWMH load, such that participants with co-occurring HIV and cannabis use had similar pvWMH load compared to controls. In addition, increased pvWMH load significantly correlated with lower cognitive performance. Our findings suggest that cannabis use does not contribute additively to WMH burden in PLWH and may potentially be associated with a reduced WMH burden. However, future work is warranted to substantiate this finding, particularly with respect to type and levels of circulating cannabinoid metabolites.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and multilevel meta-analysis of preclinical survival outcomes of Zika virus-based oncolytic therapy in glioblastoma.","authors":"Arthur Caribé Sena, Márcio Igor Santana, Vinícius Pinto Costa Rocha, Leonardo Miranda de Avellar","doi":"10.1007/s13365-026-01340-8","DOIUrl":"https://doi.org/10.1007/s13365-026-01340-8","url":null,"abstract":"<p><p>Glioblastoma remains a highly lethal primary brain tumor with limited therapeutic options. Zika virus (ZIKV) has emerged as a candidate oncolytic platform because of its tropism for glioblastoma stem-like cells and its immunomodulatory potential. We conducted a systematic review and multilevel meta-analysis of preclinical in vivo studies evaluating ZIKV-based therapy in glioblastoma. Six studies met the eligibility criteria, yielding 27 survival-relevant experimental clusters, of which 24 entered the primary quantitative synthesis. The primary analysis included 38 survival contrasts nested within 24 clusters and showed a significant pooled survival benefit within the first 25 days of follow-up (ΔRMST = 2.66 days, 95% CI 1.80-3.52; CR2 p < 0.001). Heterogeneity was substantial, and the 95% prediction interval (- 1.60 to 6.92 days) crossed the null, indicating that benefit is expected on average but not uniformly across experimental contexts. Adding therapeutic platform improved model fit, but category estimates were based on few and unevenly distributed publications; the largest point estimate, for ZIKV combined with immune checkpoint blockade (ΔRMST = 3.93 days, 95% CI 2.72-5.14; two publications), is therefore descriptive and hypothesis-generating rather than comparative evidence. Sensitivity analyses using experiment-specific truncation horizons preserved the overall direction of effect but were not directly comparable in magnitude. ZIKV-based therapy shows context-dependent preclinical activity in glioblastoma; standardized efficacy, safety, and delivery studies are required before platform selection or clinical translation.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible involvement of viral infection in the pathogenesis of myasthenia gravis.","authors":"Maria Dolci, Lucia Signorini, Federica Perego, Sara Passerini, Chiara Giannasi, Francesca Camurri, Alessia Berni, Sara Messina, Valeria Pietropaolo, Alessandro Baj, Paola Cavalcante, Serena Delbue","doi":"10.1007/s13365-026-01334-6","DOIUrl":"10.1007/s13365-026-01334-6","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is a chronic autoimmune disorder that involves the targeting of neuromuscular junctions and is primarily driven by autoantibodies against the acetylcholine receptor (AChR). While genetic susceptibility is a factor, environmental triggers, particularly viral infections, are being increasingly investigated as potential contributors to MG pathogenesis. This review examines the complex interplay between viral pathogens and MG, highlighting mechanisms such as molecular mimicry, bystander activation, and the aberrant stimulation of innate immune pathways via Toll-like receptors (TLRs). Key DNA viruses, including Epstein‒Barr virus (EBV) and parvovirus B19, have been detected within hyperplastic thymic tissues and thymomas, suggesting that they may sustain local autoreactive B-cell activation. Furthermore, recent clinical data emphasize the role of RNA viruses, most notably SARS-CoV-2, as significant triggers of new-onset MG and myasthenic crises. Despite substantial evidence linking viral infections to MG, further mechanistic research and large-scale observational studies are needed to definitively establish causality and refine therapeutic strategies targeting these virus-induced immune responses.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arboviral infections of the central nervous system: Mechanisms of invasion and long-term consequences.","authors":"Olayinka M Olajiga, Andrew G MacLean, Brandon J Beddingfield","doi":"10.1007/s13365-026-01328-4","DOIUrl":"10.1007/s13365-026-01328-4","url":null,"abstract":"<p><p>Arboviruses are a diverse group of vector-borne viruses that cause significant global morbidity and mortality. Beyond classical systemic and febrile symptoms, many arboviruses can induce a spectrum of neurological complications, ranging from mild encephalopathy to severe neuroinvasive disease. This review summarizes current knowledge on major arboviruses from the Flaviviridae, Togaviridae, Peribunyaviridae, and Reoviridae families, emphasizing mechanisms of CNS invasion, neurological manifestations, and relevant case studies or outbreaks. Mechanisms of central nervous system (CNS) invasion are highlighted, including direct viral neurotropism, blood-brain barrier crossing such as Trojan horse-mediated leukocyte trafficking and immune-mediated neuropathology. Clinical syndromes, including encephalitis, myelitis, Guillain-Barré syndrome, and movement disorders, are discussed alongside relevant case studies and outbreak reports. This review provides an integrated perspective on arbovirus-induced neurological disease for clinicians, researchers, and public health professionals.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 disrupts the integrity of a human blood-brain barrier model in the absence of infection.","authors":"Habib Jmii, Ruth Haverty, Keith D Rochfort, Nicola F Fletcher","doi":"10.1007/s13365-026-01337-3","DOIUrl":"10.1007/s13365-026-01337-3","url":null,"abstract":"<p><p>Neurological symptoms are recognized in patients with COVID-19, and include anosmia, ageusia, cognitive impairments as well as more severe complications including encephalitis and ischemic strokes. Furthermore, persistent cognitive impairment including 'brain fog' is recognised as part of the long COVID syndrome. While SARS-CoV-2 has been shown to infect cells of the central nervous system (CNS) in vitro and in vivo, it is unclear whether direct infection of the CNS or indirect mechanisms including activation of the coagulation cascade or immune activation are the key drivers of COVID-19 neuropathology. We investigated whether inactivated SARS-CoV-2, or spike protein, can disrupt the integrity of the blood-brain barrier (BBB) and characterised neuroinflammation in the absence of infection. Using an in vitro model of the BBB composed of primary human microvascular endothelial cells, astrocytes, pericytes and microglia, we observed BBB disruption following exposure of the model to SARS-CoV-2 or spike protein. Importantly, loss of BBB integrity was observed in response to luminal (mimicking 'blood side') or abluminal ('brain side') exposure to inactivated virus or spike protein. Transcriptional upregulation of a range of chemokines, inflammatory cytokines and adhesion factors, and release of inflammatory cytokines from BBB models was also observed in response to luminal or abluminal SARS-CoV-2 or spike protein exposure. These data indicate that BBB disruption and immune activation in vitro occurs in response to SARS-CoV-2 in the absence of infection, highlighting the importance of the host immune system in BBB disruption during SARS-CoV-2 infection.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chandipura virus encephalitis: an emerging pediatric neurotropic threat in india-virology, epidemiology, pathogenesis, and public health challenges.","authors":"Abdul Rahim, Md Nasiruddin Khan, Sidharth Mehan, Zuber Khan, Mustak Ahamad, Injamamul Haque","doi":"10.1007/s13365-026-01335-5","DOIUrl":"https://doi.org/10.1007/s13365-026-01335-5","url":null,"abstract":"<p><p>Chandipura virus (CHPV) is an emerging neurotropic RNA virus and member of the Rhabdoviridae family, causing outbreaks of acute encephalitis in India, mostly in children under 15 years of age. The manuscript reviews in detail the virology, genetics, clinical features, epidemiology, transmission, immunopathogenesis, and treatment of CHPV. CHPV rapidly infects neuronal tissue and activates the extrinsic pathways of neuronal apoptosis through Fas-mediated apoptosis, resulting in rapid neuronal degeneration within 24-48 h. The recent re-emergence of CHPV is another significant re-emergence in Gujarat in 2024, with the distribution of cases by space and time further suggesting CHPV is seasonal, adds new districts, and is still a threat to children. Outbreaks of CHPV typically coincide with monsoonal flooding, and Phlebotomus sandflies primarily spread the disease. The monsoonal flooding and environmental degradation that occurred during the breeding season, rendering sandflies more susceptible to outbreaks, are remarkable. Differentiation of other encephalitic viruses, such as Japanese encephalitis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and dengue, is important for clinical diagnosis and also because of the rapid progression of CHPV. Several points to consider are low CSF pleocytosis and the neuroimaging characteristics that are identifiable. The immune response after infection is marked by a cytokine storm, followed by lymphocyte apoptosis and reduction in CNS viral clearance. Over the past decade, laboratories in India have developed in the realm of diagnosis and treatment of CHPV with the advent of molecular diagnostics such as real-time RT-PCR and IgM ELISA. However, a lack of a licensed vaccine and antivirals would make this new infectious disease more difficult to manage. This review highlights the critical importance of further surveillance, vector control, public health preparedness, and vaccine development/therapeutics for CHPV.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 5","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oropouche virus infection and neurological involvement: a hypothesis-generating neuroimmune framework.","authors":"Nohora Cristina Ayola-Serrano, Christian Ayola","doi":"10.1007/s13365-026-01331-9","DOIUrl":"10.1007/s13365-026-01331-9","url":null,"abstract":"<p><p>Oropouche virus (OROV), an emerging orthobunyavirus in the Americas, has historically been associated with self-limited febrile illness in endemic Amazon basin regions. However, recent epidemiological updates from the Pan American Health Organization (PAHO) and World Health Organization (WHO) document a marked increase in case counts and geographic expansion, with over 16,000 confirmed cases reported in 2024 and continued transmission across multiple countries in 2025, including regions where transmission had not been previously recognized. The detection of cases in the Caribbean, Central America, and imported infections in North America and Europe underscores its evolving epidemiological profile and growing global relevance. In parallel with this expansion, neurological involvement-including meningitis and encephalitis-has been reported in a subset of patients. Experimental and ex vivo studies demonstrate neural permissiveness and suggest the capacity for interaction with central nervous system (CNS) tissue. Based on established principles of viral neuroimmunology, a conservative conceptual framework is proposed linking acute neuroimmune activation during OROV infection to potential neurological manifestations. Although long-term neurological sequelae have not been systematically characterized, existing clinical observations and biological mechanisms provide plausibility for further investigation. This framework is intended to generate testable hypotheses and guide prospective studies rather than establish causality.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: rare progressive cavitary lesion in progressive multifocal leukoencephalopathy.","authors":"Mindy Hoang, Richard Hc Lai","doi":"10.1007/s13365-026-01326-6","DOIUrl":"10.1007/s13365-026-01326-6","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by reactivation of John Cunningham (JC) virus in a subset of immunocompromised individuals. This case report describes a rare case of progressive cavitary lesion in PML with only one other documented case in the world. The patient is a 63-year old male with medical history of microscopic polyangiitis who had previously undergone cyclophosphamide treatment and was on chronic immunosuppression with mycophenolate and high dose prednisone who presented to the emergency department with stroke-like symptoms. A series of magnetic resonance imaging (MRI) demonstrated a non-enhancing multifocal lesion in his frontal lobe that progressed into a cavitary lesion. PML was diagnosed using imaging presence of periventricular white matter lesions and positive JC virus in the cerebrospinal fluid. Stereotactic biopsy followed by histological staining of the samples and immunohistochemistry confirmed the diagnosis. We emphasize cavitary lesions as an extremely rare, but potential development of PML that appears to correlate with aggressive neurocognitive decline and has no identified associations.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}