Brita Ostermeier, Clarissa Halpern, Sanjay B Maggirwar
{"title":"Regulation of eco-tropic human immunodeficiency virus type-1-infection by sterile alpha motif and histidine-aspartic domain containing protein-1 in a microglial cell line: a novel in vitro model for studying HIV infection and latency in microglia.","authors":"Brita Ostermeier, Clarissa Halpern, Sanjay B Maggirwar","doi":"10.1007/s13365-025-01280-9","DOIUrl":"https://doi.org/10.1007/s13365-025-01280-9","url":null,"abstract":"<p><p>Microglia are considered the main human immunodeficiency virus (HIV) reservoirs in the central nervous system (CNS) due to their ability to become productively infected, produce new infectious HIV virions, and support HIV latency. The anatomical location of microglia necessitates the use of in vitro HIV infection models. However, currently available in vitro models are laced with limitations, including their suboptimal HIV infection rates, poor experimental tractability, and low affordability. Therefore, we sought to develop a new in vitro infection model that addresses these concerns. Here, we confirmed that microglia express sterile alpha motif and histidine-aspartic domain-containing protein-1 (SAMHD1), an antiviral mechanism that opposes HIV replication. We show that administration of simian immunodeficiency virus (SIV)-derived Vpx virus-like particles (VLPs) can reduce the levels of SAMHD1, thus allowing for increased infectivity in EcoHIV-infected CHME5 microglial cell line. With this model, we achieved higher initial rates of HIV infection. We could also track the cells using eGFP expression during active replication, latency, and latency reversal. Further, we developed a CHME5-EcoHIV + cell line using fluorescence-activated cell sorting (FACS). Despite high infectivity of HIV in CHME5 cells, we confirmed that limited latency reversal occurs following their exposure to conventional latency reversing agents (LRAs). Our novel microglia infection model saves researchers time and money and, due to its ease of use, can rapidly contribute to curative research in the field.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337214","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}
Linn Renborg, Aylin Yilmaz, Staffan Nilsson, Henrik Zetterberg, Kaj Blennow, Magnus Gisslén
{"title":"Rapid decline of cerebrospinal fluid biomarkers of axonal injury and neuroinflammation after initiation of antiretroviral therapy in HIV.","authors":"Linn Renborg, Aylin Yilmaz, Staffan Nilsson, Henrik Zetterberg, Kaj Blennow, Magnus Gisslén","doi":"10.1007/s13365-025-01287-2","DOIUrl":"https://doi.org/10.1007/s13365-025-01287-2","url":null,"abstract":"<p><p>Persistent intrathecal immune activation and neuronal injury remain common in people with HIV (PWH) despite effective antiretroviral therapy (ART). We examined longitudinal trajectories of cerebrospinal fluid (CSF) neurofilament light (NfL), a marker of axonal injury, together with neuroinflammatory biomarkers following ART initiation. Ninety-nine PWH from the Gothenburg HIV CSF Study Cohort who achieved viral suppression were included, with CSF samples collected before and after treatment initiation. NfL and a panel of biomarkers including YKL-40, sTREM-2, neopterin, and GFAP were analyzed. CSF NfL declined rapidly, from a mean of 673 ng/L at baseline to 592 ng/L after three months and 490 ng/L after twelve months. All inflammatory biomarkers showed parallel and significant decreases. Prior to ART, 25% of participants had elevated NfL levels; this subgroup displayed higher baseline inflammation, and the steepest biomarker declines after treatment initiation. In participants with normal baseline NfL, inflammatory markers decreased while NfL remained stable. Beyond one year, no further reductions were evident. These longitudinal findings demonstrate that ART rapidly and effectively reduces CSF biomarkers of neuronal injury and neuroinflammation in HIV, with the greatest benefit in individuals with baseline axonal damage.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345891","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":"The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.","authors":"Melika Amelimojarad, Mandana Amelimojarad","doi":"10.1007/s13365-025-01282-7","DOIUrl":"https://doi.org/10.1007/s13365-025-01282-7","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2), a key regulator of the renin-angiotensin system (RAS), maintains central nervous system (CNS) homeostasis by metabolizing neuroinflammatory peptides like angiotensin II (Ang II) and apelin-13, thereby exerting neuroprotective effects. Recent evidence underscores ACE2's paradoxical roles in neurodegeneration: its loss of function due to SARS-CoV-2 spike protein binding exacerbates neuroinflammation and cognitive decline, while its upregulation may mitigate AD pathology by reducing amyloid-β (Aβ) accumulation and tau hyperphosphorylation. The COVID-19 pandemic has further highlighted ACE2 axis dysregulation as a potential accelerator of AD progression, with studies reporting elevated biomarkers of neurodegeneration in post-COVID patients. Therefore, in this review, we highlight the emerging insights into ACE2's dual role in AD and other neurodegenerative diseases, emphasizing its interactions with microglial activation, blood-brain barrier integrity, and mitochondrial dysfunction. We also critically evaluate novel therapeutic strategies, including recombinant ACE2, ACE2-derived peptides, and gene therapy approaches designed to restore RAS balance without compromising viral defense mechanisms. By integrating mechanistic and clinical insights, this work highlights ACE2 as a promising target for neurodegenerative disease interventions.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292512","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}
Ninghao Chen, Bo Wang, Zhenbin Zhan, Hai Chen, Jinguang Chen, Ye Cai
{"title":"The protective role of dexmedetomidine against anaesthetics-induced neurotoxicity through downregulating miR-34a.","authors":"Ninghao Chen, Bo Wang, Zhenbin Zhan, Hai Chen, Jinguang Chen, Ye Cai","doi":"10.1007/s13365-025-01281-8","DOIUrl":"https://doi.org/10.1007/s13365-025-01281-8","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292576","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":"Spatial and temporal mapping of early alphaherpesvirus invasion routes into the mouse central nervous system.","authors":"Viktoria Korff, Issam El-Debs, Julia Sehl-Ewert","doi":"10.1007/s13365-025-01278-3","DOIUrl":"https://doi.org/10.1007/s13365-025-01278-3","url":null,"abstract":"<p><p>Alphaherpesviruses such as Herpes Simplex Virus 1 (HSV-1) and Pseudorabies virus (PrV) invade the central nervous system (CNS) via peripheral nerves. While olfactory and trigeminal pathways are well-known, additional cranial routes remain underexplored. Using a PrV-∆UL21gfp/US3∆kin mutant in CD1 mice, we mapped early neuroinvasion (4-96 hpi) by immunofluorescence and RNA in situ hybridization. Viral antigen and lytic viral gene expression (UL19 RNA) were detected in the olfactory epithelium, vomeronasal organ, incisors, palate, olfactory bulb, and brainstem. These results indicate multineural CNS access involving olfactory (I), trigeminal (V), glossopharyngeal (IX), and hypoglossal (XII) nerves, highlighting this model's value for studying early alphaherpesvirus spread.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185851","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}
Sara Passerini, Sara Messina, Marta De Angelis, Lucia Nencioni, Francesca Gianno, Manila Antonelli, Valeria Pietropaolo
{"title":"Correction: The presence of human polyomavirus JC (JCPyV) in pediatric brain tumors: a plausible trigger in Wnt/β-catenin pathway.","authors":"Sara Passerini, Sara Messina, Marta De Angelis, Lucia Nencioni, Francesca Gianno, Manila Antonelli, Valeria Pietropaolo","doi":"10.1007/s13365-025-01284-5","DOIUrl":"https://doi.org/10.1007/s13365-025-01284-5","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176074","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}
Sara Passerini, Sara Messina, Marta De Angelis, Lucia Nencioni, Francesca Gianno, Manila Antonelli, Valeria Pietropaolo
{"title":"The presence of human polyomavirus JC (JCPyV) in pediatric brain tumors: a plausible trigger in Wnt/β-catenin pathway.","authors":"Sara Passerini, Sara Messina, Marta De Angelis, Lucia Nencioni, Francesca Gianno, Manila Antonelli, Valeria Pietropaolo","doi":"10.1007/s13365-025-01274-7","DOIUrl":"10.1007/s13365-025-01274-7","url":null,"abstract":"<p><p>JC polyomavirus (JCPyV) is associated with progressive multifocal leukoencephalopathy (PML), but its plausible role in brain cancers is also disputed. One candidate to mediate cell transformation is the Large T antigen (LTAg), which has the capability to bind the Wnt pathway protein β-catenin, thus deregulating the cell cycle. In the current study, we investigated the presence and molecular state of JCPyV in pediatric brain tumors and the effects of virus-positivity on the Wnt pathway. JCPyV DNA was found in 31/101 (30.7%) brain tumors with a viral load of 3.2 copies/cell. The amplified NCCR revealed an archetype sequence, and VP1 reported a high degree of homology with the reference strain. The LTAg gene was reported in all JCPyV-positive tumors. Interestingly, among them, 5 tissues did not express VP1 and viral miRNAs, supporting a hampering of late region transcription. Over-expression of β-catenin, c-myc and cyclin D1 was observed in JCPyV-positive tissues compared to negative ones, suggesting that the virus may exploit this signaling pathway, potentially contributing to brain carcinogenesis. The current study adds further evidence of JCPyV prevalence in human brain tumors and reports alterations of the Wnt pathway, laying the basis for further investigation on JCPyV-mediated oncogenesis in the brain.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075508","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}
Aleksandra Đ Ilić, Vladimir Galić, Vojislava Bugarski Ignjatović, Željka Nikolašević, Dmitar Vlahović, Goran Knezović, Jasmina Boban, Duško Kozić, Željko Živanović
{"title":"Cognitive and vascular (dys)function after COVID-19.","authors":"Aleksandra Đ Ilić, Vladimir Galić, Vojislava Bugarski Ignjatović, Željka Nikolašević, Dmitar Vlahović, Goran Knezović, Jasmina Boban, Duško Kozić, Željko Živanović","doi":"10.1007/s13365-025-01276-5","DOIUrl":"https://doi.org/10.1007/s13365-025-01276-5","url":null,"abstract":"<p><p>COVID-19 is a systemic infection that causes endothelial dysfunction, contributing to severe cases. While vascular complications are well-documented, their impact on vascular structure, function, and cognition remains unclear. This cross-sectional study explored vascular and cognitive differences across patients with mild, moderate, and severe COVID-19, examining correlations between global cognitive performance and vascular parameters. This study included 83 working-age patients (30-65 years, both sexes) who recovered from COVID-19 within 6-12 months. They were grouped by severity: mild (outpatients, no oxygen support), moderate (hospitalized, conventional oxygen therapy), and severe (hospitalized, advanced oxygen therapy). Exclusions included pre-existing cognitive or neurological conditions, significant atherosclerosis, malignancies, and prior COVID-19 vaccination. Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test, while vascular parameters - carotid intima-media thickness (IMT), beta stiffness index (β index), mean flow velocity (MVs), maximum velocity after breath-holding (MV-BH), and breath-holding index (BHI) - were evaluated using duplex ultrasound and transcranial Doppler. Patients with severe COVID-19 had the highest carotid stiffness and poorest cerebrovascular reactivity. While MoCA scores showed no significant group differences, 23-40% had mild cognitive impairment. MoCA scores negatively correlated with β index in mild group (ρ=--0.453; p = 0.034), while MVs positively correlated with MoCA in severe cases (ρ = 0.414; p = 0.028). The association between arterial stiffness and cognitive impairment in mild cases, suggests lasting effects of SARS-CoV-2 rather than pre-existing conditions. These findings highlight carotid stiffness as a key factor in post-COVID-19 cognitive impairment, emphasizing early risk identification for timely intervention.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065063","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}
Merle Henderson, Kate Alford, Samira Bouyagoub, Nicki Doyle, Sriram Vundavalli, Pedro Vicente, Albert Busza, Alan Winston, Jaime H Vera
{"title":"Changes in cerebral function parameters in persons with HIV with symptoms of insomnia switching from dolutegravir- to bictegravir-based antiretroviral therapy.","authors":"Merle Henderson, Kate Alford, Samira Bouyagoub, Nicki Doyle, Sriram Vundavalli, Pedro Vicente, Albert Busza, Alan Winston, Jaime H Vera","doi":"10.1007/s13365-025-01270-x","DOIUrl":"https://doi.org/10.1007/s13365-025-01270-x","url":null,"abstract":"<p><p>Sleep disturbances are frequently reported in persons with HIV and have been associated with the use of certain integrase strand transfer inhibitors (INSTIs), such as dolutegravir. This exploratory study assessed changes in cerebral function parameters in individuals with insomnia switching INSTIs. Individuals with an insomnia severity index (ISI) above 8 and virologically suppressed on a dolutegravir-containing ART regimen (DTG-ART) were randomised 1:1 to either continue DTG-ART or switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC-ART) for 120 days. Cerebral function parameters were measured longitudinally at baseline (D0) and day 120 (D120) and included: (1) patient-reported outcomes (PROs) assessing sleep, quality of life (QoL) and symptoms related to ART, (2) resting-state functional cerebral MRI (fMRI), examining functional connectivity networks previously associated with DTG use or sleep and (3) plasma soluble inflammatory biomarkers associated with neuroinflammation or HIV disease progression (Neopterin, CXCL10 and IL-6). Functional connectivity analyses were performed using Seed-Based Correlations (SBC), and correlations between connectivity changes, PRO measures and biomarker concentrations determined. Of 19 individuals (12 DTG-ART, 7 BIC-ART), median age was 55 years (range 28-83), all were male and 17 of white ethnicity. Over 120 days, improvements in sleep and QoL in those randomised to BIC-ART vs. DTG-ART were observed. Median change in Insomnia Severity Index (ISI) score - 9 (-14 to -2) vs. -1 (-10 to -4), p = 0.030, Epworth Sleepiness Scale (ESS) -3.0 (-6 to -1) vs. 2 (-3 to 6), p = 0.007 and Short Form-36 Physical Function (SF36-PF) -5 (-40 to 5) vs. 0 (-5 to 15), p = 0.026) for BIC- vs. DTG- ART, respectively. BIC-ART was also associated with increased functional connectivity in the Default Mode and Salience Networks (both p < 0.05), which correlated with improvements in PRO measures (ESS and SF36-PF, both p < 0.05). No significant changes in soluble biomarkers were observed. Individuals with insomnia switching to BIC-ART had improvements in self-reported sleep, QoL and resting state fMRI networks associated with sleep, when compared to those continued on DTG-ART.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957576","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}
Journal of NeuroVirologyPub Date : 2025-08-01Epub Date: 2025-06-05DOI: 10.1007/s13365-025-01261-y
Sidharth S, Sarada Devi K L, Sreelatha K H
{"title":"Clinical spectrum of AES (Acute encephalitis syndrome) and a syndromic approach for its diagnosis.","authors":"Sidharth S, Sarada Devi K L, Sreelatha K H","doi":"10.1007/s13365-025-01261-y","DOIUrl":"10.1007/s13365-025-01261-y","url":null,"abstract":"<p><p>Acute encephalitis syndrome (AES) is now being used for surveillance in all encephalitis endemic zones irrespective of the etiology. Numerous viral pathogens possess the ability to invade the CNS and produce neurologic dysfunction. We performed a hospital-based descriptive study between January 2019 to January 2020 in the Department of Microbiology, GMC, Thiruvananthapuram taking samples from 193 AES patients admitted under the Departments of Internal Medicine, Neurology & Paediatrics. The samples were proceeded with PCR/ELISA depending on the clinical history. A viral etiology was established in 48 cases (24.9%) & most were caused by EBV (5.7%). MRI revealed temporal lobe involvement in 9 patients. 20% cases had post-encephalitic sequelae-focal neurological deficits and persistent seizures. Most number of patients were found to have infected with Epstein- Barr virus. Identification of the causative agent is of great importance in AES, as rapid detection and confirmation of etiological agent will have a tremendous impact on the management of outbreaks as well as patient's disease.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"363-375"},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225767","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}