Journal of NeuroVirology最新文献

{"title":"Neuropathogenesis of Usutu virus-associated disease in Eurasian blackbirds (Turdus merula) involves apoptosis through the extrinsic pathway.","authors":"Giuseppe Giglia, Gianfilippo Agliani, Bas B Oude Munnink, Reina S Sikkema, Maria Teresa Mandara, Christine Fast, Marleen Gosens, Eefje J A Schrauwen, Erwin de Bruin, Andrea Gröne, Judith M A van den Brand","doi":"10.1007/s13365-025-01302-6","DOIUrl":"10.1007/s13365-025-01302-6","url":null,"abstract":"<p><p>Usutu virus (USUV) is a zoonotic arbovirus causing systemic and neuroinvasive diseases in birds and flu-like or sporadic neuroinvasive disease in humans. USUV-associated encephalitis is morphologically well-characterized in birds, while the mechanisms of cell-damage in spontaneously infected birds remain poorly understood. For the closely related West Nile virus, apoptosis significantly contributes to the pathogenesis of othoflavivirus-induced neuropathology. This study investigates the involvement of apoptosis in USUV-associated encephalitis in Eurasian blackbirds (Turdus merula). To determine the apoptosis involvement, immunohistochemistry for cleaved-caspase-3 (CC3), TUNEL-assay, and RT-qPCR to compare mRNA expression levels of caspase 8 (extrinsic pathway) and caspase 9 (intrinsic pathway) were performed on brains of USUV-infected (n = 26) and USUV-uninfected (n = 16) blackbirds, as well as Africa 3 and Europe 3 USUV-lineages. The results showed a higher CC3 expression in USUV-infected (m = 231,96 ± 117,033) compared to uninfected blackbirds (m = 22,00 ± 13,31) (p < 0.001). Similarly, higher TUNEL-positive cell counts were detected in USUV-infected (m = 197,00 ± 83,56) compared to uninfected blackbirds (m = 19,00 ± 16,08) (p < 0.01). No significant differences were detected comparing Africa 3 and Europe 3 lineages. Additionally, both caspases were upregulated in USUV-infected blackbirds. Caspase 8 was in average 4,37 ± 0,89 (CI α = 0,05) times higher in USUV-infected blackbirds (p < 0.0001), while caspase 9 expression was in average 1,82 ± 0,89 (CI α = 0,05) times higher in USUV-infected blackbirds (p < 0.01). Although both apoptotic pathways are involved, the extrinsic pathway is notably more active in USUV-infected blackbirds, highlighting its role in USUV-associated brain damage.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344378","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":"Bell's palsy as the initial manifestation of Listeria monocytogenes rhombencephalitis with brainstem abscesses in an immunocompetent adult: a case report.","authors":"María Camila Castañeda-Gómez, Valeria Ortegón-Ayala, Miguel Romero, Jose Luis Bustos","doi":"10.1007/s13365-025-01300-8","DOIUrl":"https://doi.org/10.1007/s13365-025-01300-8","url":null,"abstract":"<p><p>Listeria monocytogenes (LM) rhombencephalitis is a rare but severe manifestation of neurolisteriosis, typically reported in immunocompromised or elderly patients and often associated with high morbidity and mortality. We describe a 66-year-old immunocompetent man who presented initially with peripheral facial paralysis, an uncommon early manifestation reflecting cranial neuritis, before rapidly developing brainstem dysfunction, respiratory failure, and multiple abscesses. Diagnosis was confirmed by cerebrospinal fluid (CSF) multiplex polymerase chain reaction (PCR) and blood cultures, and despite targeted antimicrobial therapy the patient developed severe neurological sequelae. This case underscores that cranial neuritis may present as an early clue of neurolisteriosis.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344180","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":"Serum but not cerebrospinal fluid biomarkers are associated with domain-specific cognitive performance in PWH.","authors":"Elisa Vuaran, Mattia Trunfio, Marco Russo, Miriam Antonucci, Jessica Cusato, Daniela Vai, Cristiana Atzori, Daniele Imperiale, Stefano Bonora, Andrea Calcagno","doi":"10.1007/s13365-025-01288-1","DOIUrl":"https://doi.org/10.1007/s13365-025-01288-1","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344436","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":"Z-DNA binding protein 1 mediates necroptotic cell death in primary murine microglia following herpes simplex virus-1 infection.","authors":"Alexander J Suptela, Ian Marriott","doi":"10.1007/s13365-025-01304-4","DOIUrl":"10.1007/s13365-025-01304-4","url":null,"abstract":"<p><p>The mechanisms by which microglia respond to viral central nervous system (CNS) pathogens are now becoming apparent with the demonstration that they express an array of pattern recognition receptors that include cytosolic sensors for exogenous nucleic acids. We have previously shown that microglia express Z-DNA binding protein 1 (ZBP1) and found that this sensor contributes to their inflammatory responses to the clinically relevant DNA virus, herpes simplex virus-1 (HSV-1). More recently, we showed that ZBP1 serves as a restriction factor for HSV-1 in murine astrocytes and is associated with the induction of both necroptotic and apoptotic cell death pathways in these cells. Here, we demonstrate that this cytosolic DNA sensor similarly functions as a HSV-1 restriction factor in primary murine microglia. However, unlike astrocytes, we have determined that a neuroinvasive clinically-derived HSV-1 isolate induces necroptosis, but not apoptosis, in these myeloid cells in a ZBP1-dependent as well as a ZBP1-independent manner. Interestingly, we found that a laboratory adapted HSV-1 strain elicits microglial apoptosis in a ZBP-1-independent manner, in addition to both ZBP1-dependent and independent necroptosis, indicating that viral strain-specific differences may exist. However, it remains to be seen whether ZBP1-mediated cell death in microglia contributes significantly to host protection or, rather, exacerbates DNA virus-associated CNS pathology in mice.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344455","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":"Breaking down barriers in Zika virus research: progressing immune pathogenesis research, international cooperation, and data sharing for preparedness.","authors":"Vishavjeet Singh, Ahire Chetan Uddhav, Bikash Kumar Sah, Ankit Kumar","doi":"10.1007/s13365-025-01289-0","DOIUrl":"https://doi.org/10.1007/s13365-025-01289-0","url":null,"abstract":"","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344206","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":"CSF CXCL13 as a longitudinal marker for neurocognition in HIV-1-associated dementia after start of treatment in cART-naïve patients.","authors":"Jürgen Panholzer, Anna R Tröscher, Vincent Böhm, Raimund Helbok, Christian Eggers","doi":"10.1007/s13365-025-01293-4","DOIUrl":"https://doi.org/10.1007/s13365-025-01293-4","url":null,"abstract":"<p><p>Despite suppression of viral replication by antiretroviral therapy (cART) HIV-associated neurocognitive disorders (HAND) may persist. This involves chronic inflammation with activation of the monocyte-macrophage-microglia axis. We examined CXCL13, a chemokine released by these cells, as a possible marker for HAND treatment response. We longitudinally analyzed cerebrospinal fluid (CSF) from before and during newly initiated cART of people living with HIV (PLWH) with HIV-associated dementia (HAD). CXCL13_CSF was determined by ELISA. We studied the correlation of CXCL13_CSF with HAD as measured by the Memorial Sloan Kettering score (MSK-score) and with CSF and blood parameters. Twelve treatment-naïve patients with HAD were included. Prior to cART the correlation of CXCL13_CSF (τ_b = 0.575, p = 0.051) with MSK-score narrowly missed significance. At an average of 2,9 months after start of cART, CXCL13_CSF strongly correlated with MSK-score (τ_b = 0.746, p = 0.005). Also, the magnitude of the longitudinal change of CXCL-13_CSF correlated with the change of MSK-score (τ_b = 0.460, p = 0.048). No correlation was found between MSK-score and CSF white blood cell count (WBC_CSF) as well as HIV-RNA (plasma, CSF). CXCL13_CSF showed a significant correlation with HAD but not with WBC_CSF and HIV-RNA. As CXCL13 in the CNS is secreted by macrophages and microglia our results suggest a significant role of the monocyte-macrophage-microglia axis as a line of immunological defense relatively independent of viral replication. If supported by further studies CXCL13 might serve as CSF biomarker in HIV patients with HAD.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344297","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":"Chronic granulomatosis with persistent HSV intrathecal synthesis over three years: a rare complication of HSV encephalitis in adult.","authors":"M Mauclin, G Fargeot, G Nasser, A-A Mariaggi, J-B Brunet de Courssou","doi":"10.1007/s13365-025-01298-z","DOIUrl":"https://doi.org/10.1007/s13365-025-01298-z","url":null,"abstract":"<p><p>A 62-year-old man developed HSV-1 encephalitis with involvement of the left fronto-temporal lobes and caudate nucleus, improving under acyclovir. One month later, he developed mild word-finding difficulty. MRI showed the emergence of ring-enhancing nodular lesions with surrounding edema, confined to previously affected areas. Extensive repeat investigations revealed no alternative diagnosis. The patient recovered and remained clinically stable during follow-up. MRI over three years showed slow regression of the nodular lesions. A lumbar puncture at 3.5 years confirmed ongoing intrathecal immunoglobulin synthesis, with HSV-1-specific intrathecal synthesis. This case illustrates a rare post-herpetic granulomatous evolution, previously reported in only a few adults.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344274","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":"NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.","authors":"Benjamin Weller, Chung-Wen Lin, Simin Rothballer, Michael A Calderwood, Pascal Falter-Braun, Claudia Falter","doi":"10.1007/s13365-025-01303-5","DOIUrl":"10.1007/s13365-025-01303-5","url":null,"abstract":"<p><p>Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344448","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":"Limbic and whole-brain functional connectivity in non-substance abusers with human immunodeficiency virus (HIV).","authors":"Stuart D Washington, Anisa Thomas, Kehinde Omisore, Cedric Cole, Tomilowo Abijo, Ashley VanMeter, Marjorie C Gondré-Lewis","doi":"10.1007/s13365-025-01301-7","DOIUrl":"https://doi.org/10.1007/s13365-025-01301-7","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) negatively impacts behavioral health and is co-morbid with neurocognitive and psychiatric disorders, most notably substance use disorder (SUD). Neuroimaging studies repeatedly show diminished functional connectivity in people living with HIV (PLWH). However, previous studies appear to disregard any potential for HIV/SUD co-morbidities, an oversight that represents a potential confound in HIV-related neuroimaging literature. Further, the functional connectivity of limbic neural substrates underlying reward and SUD (e.g., nucleus accumbens, amygdala, and hippocampus) remain unexplored in HIV. Here, we obtained resting-state functional magnetic resonance imaging (rsfMRI) data from a small population of HIV-positive people with no history of SUD. Functional connectivity in people with HIV was generally reduced relative to controls, with the greatest differences occurring between visual cortex and cerebellar vermis and nodules also associated with non-motor functions of cerebellum. Seed-based analyses of left and right nucleus accumbens (NAcc) and hippocampus (Hippo) yielded robust connections with the default mode network in controls. In PLWH, connectivity between NAcc or Hippo as seed recruited the default mode and inferior temporal networks to a lesser extent. Similar seed-based analyses of the amygdala in controls yielded robust connections with inferior temporal lobe regions rather than the default mode network, and exhibited anti-correlations with the executive network. Our results suggest that (1) people with HIV and no SUD history show reduced overall functional connectivity relative to controls, consistent with previous rsfMRI studies of people with HIV, and (2) this reduced connectivity in people with HIV extends to limbic structures underlying reward, even in the absence of SUD.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290250","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":"Unmasking HAM/TSP: understanding HTLV-1-driven neurological disease.","authors":"Arash Letafati, Saeed Tajik, Mona Vasei Rad, Ramin Shahbahrami, Melina Moulaeian, Mehdi Norouzi, Sayed-Hamidreza Mozhgani","doi":"10.1007/s13365-026-01305-x","DOIUrl":"10.1007/s13365-026-01305-x","url":null,"abstract":"<p><p>Human T-cell Lymphotropic virus type 1 (HTLV-1) is a retrovirus that infected 10-20 million of individuals worldwide. HTLV-1 infection is associated with the development of various diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). HAM/TSP is a chronic progressive neuroinflammatory disease characterized by motor impairment, spasticity, and other neurological manifestations. This narrative review provides a comprehensive overview of HAM/TSP following HTLV-1 infection. We discussed the virology and epidemiology of HTLV-1, transmission modes, and risk factors for infection. Furthermore, we delved into the pathogenesis of HAM/TSP disease, exploring the role of neuroimmunology and immune dysregulation. Viral proteins and host genetic factors that influence disease progression are also examined. Diagnostic approaches, including laboratory tests and imaging techniques, are discussed, along with available treatment options and immunomodulatory therapies. Additionally, we highlighted the history of HAM/TSP disease and provide insights into the global distribution and epidemiology. Finally, the current status and challenges of HTLV-1 vaccine development are addressed. This narrative review aims to enhance understanding of HAM/TSP disease following HTLV-1 infection, shedding light on key aspects of their etiology, diagnosis, and management, while emphasizing the need for continued research and public health interventions.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":"32 2","pages":"8"},"PeriodicalIF":1.9,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227181","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}