Search Results (390)

SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens. Full article

Neonatal meningitis-associated Escherichia coli (NMEC) is a formidable pathogen in veterinary medicine. The emergence of atypical, multidrug-resistant (MDR) variants complicates disease control. An Escherichia coli (E. coli) strain was isolated from the brain tissue of a deceased calf with acute meningitis. Comprehensive characterizations were performed, including whole-genome sequencing (WGS), multi-locus sequence typing (MLST), antimicrobial susceptibility testing (AST), murine pathogenicity assays, and RT-qPCR evaluation of neuroinflammatory cytokines. Results: The isolate (O18ab:H14) was identified as a capsule-deficient NMEC strain belonging to phylogroup A and sequence type ST1434. WGS showed that the genome size of this strain is 5.1 Mb, containing 73 strictly defined antimicrobial resistance genes and 202 virulence factors. These may be involved in the compensatory mechanism for capsule deficiency, and further functional verification is required. Phenotypically, it exhibited a robust MDR profile. In the murine model, the strain demonstrated high lethality, and induced severe multi-organ lesions characteristic of both meningitis and systemic sepsis. While intraperitoneal injection bypasses natural colonization routes, the brain-specific bacterial persistence and neuronal pathology imply neurotropic potential. Furthermore, RT-qPCR confirmed a severe neuroinflammatory response, marked by the significant upregulation of IL-1β, IL-6, and TNF-α in the infected brains. This study characterizes a novel, highly virulent, and MDR capsule-deficient NMEC/SEPEC hybrid strain. The findings emphasize the urgent need for continuous genomic surveillance of atypical E. coli pathotypes in livestock. Full article

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection. Full article

Bornaviruses are neurotropic, negative-sense RNA viruses with zoonotic potential, notably Borna disease virus 1 (BoDV-1) and variegated squirrel bornavirus 1 (VSBV-1). BoDV-1 is endemic in certain regions of Central Europe and maintained in bicolored white-toothed shrews, but its presence in Croatia has not been investigated. Given Croatia’s diverse biogeography and the prevalence of rodent-borne diseases, this study aimed to investigate the presence of orthobornaviruses in wild canids and mustelids. Brain samples from red foxes (Vulpes vulpes), golden jackals (Canis aureus moreoticus), wolves (Canis lupus), martens (Martes martes) and badgers (Meles meles) were analysed using pan-bornavirus RT-PCR. Despite successful RNA extraction and internal control amplification, bornavirus RNA was not detected in any of the 860 animal samples tested. Although no orthobornavirus RNA was detected, the results still provide valuable information: bornavirus infections appear to be absent or extremely rare in Croatian wild canids and mustelids. By excluding these species as current potential reservoir hosts, this study helps to refine the geographical extent of bornavirus endemicity and emphasises the importance of continuous One Health surveillance in regions with favourable ecological conditions for zoonotic spillover. Full article

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming—particularly involving lipid and sphingolipid metabolism—was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development. Full article

The neuroinvasive and neurotropic character of coronaviruses is a likely reason for neurological complications which may occur during acute COVID illness and sometimes persist or newly emerge in the post-acute phase. Terminology and temporal classification remain heterogeneous. A retrospective case series was conducted in a single center (Department of Neurology, Bielański Hospital, Warsaw, Poland). Medical records from March 2020 to December 2023 were screened. Inclusion criteria: (1) confirmed SARS-CoV-2 infection (polymerase chain reaction or antigen test and radiological findings), (2) new neurological syndrome within acute, post-acute, or post-COVID interval, and (3) diagnostic documentation. Exclusion criteria: alternative established etiology fully explaining the neurological condition. Six cases were selected for detailed analysis due to diagnostic completeness as well as etiological and temporal diversity. Cases included: (1) persistent neurocognitive and sensory symptoms (post-COVID), (2) acute ischemic stroke with internal carotid artery dissection during severe COVID-19, (3) cytotoxic lesion of the corpus callosum (CLOCC) during acute COVID-19, (4) Guillain–Barré syndrome (post-acute), (5) longitudinally extensive transverse myelitis (post-acute), and (6) delayed autoimmune cerebral vasculitis (post-COVID). Neurological presentations ranged from mild persistent symptoms to fatal outcome. Neurological complications span inflammatory, vascular, and autoimmune mechanisms across distinct temporal phases of SARS-CoV-2 infection. Precise temporal classification and systematic diagnostic protocols are essential. Prospective longitudinal studies integrating biomarkers and standardized neuroimaging are required. Full article

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk. Full article

The coronavirus disease 2019 (COVID-19) pandemic has been associated with a wide range of neurological complications, among which persistent cognitive impairment and memory deficits are increasingly recognized as key symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID). Although clinical and epidemiological studies have documented these symptoms across diverse patient populations, the underlying neurobiological mechanisms remain incompletely understood. Growing evidence from human studies, neuropathological analyses, and experimental models indicates that neuroimmune and inflammatory processes plays a central role in COVID-19-associated cognitive dysfunction. As the brain’s resident immune cells, microglia are vital for synaptic health, neuroplasticity, and memory, yet these processes may be compromised after SARS-CoV-2 infection. Systemic inflammation, blood–brain barrier (BBB) disruption, endothelial injury, and cytokine signaling can induce sustained microglial activation and priming, leading to inflammasome activation, complement-mediated synaptic remodeling, oxidative stress, and impaired hippocampal neurogenesis. These processes collectively disrupt neural circuits involved in learning and memory and may underlie the persistent “brain fog” reported by COVID-19 survivors. This review synthesizes clinical, biomarker, neuroimaging, and mechanistic evidence linking SARS-CoV-2 infection to microglia-mediated neuroinflammation and memory impairment. In contrast to prior reviews that broadly describe neuroinflammation in COVID-19, we integrate multidimensional evidence into a microglia-centric immunovascular framework that highlights converging pathogenic pathways underlying cognitive symptoms. We further discuss emerging biomarkers of glial activation and evaluate current and prospective therapeutic strategies targeting microglial and neuroimmune pathways. Understanding the role of microglial dysregulation in post-COVID cognitive impairment may facilitate the development of targeted interventions to mitigate long-term neurological consequences of COVID-19. Full article

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that interacts dynamically with host cells within structured tissue environments. Conventional two-dimensional (2D) cultures do not fully recapitulate these spatial and microenvironmental features. In this study, we established a three-dimensional (3D) culture system using the self-assembling peptide RADA16-I to generate an extracellular matrix–mimetic hydrogel scaffold. This platform supported the formation of stable Vero cell spheroids that remained viable for more than 30 days. Following HSV-1 infection, viral spread initiated at the spheroid periphery and progressively extended toward the core. Sustained viral replication was detected for up to 22 days, indicating long-term maintenance of infection within the 3D structure. Ultrastructural examination identified viral particles and vesicular compartments consistent with autophagy-related organelles. Comparative analysis of autophagy-associated markers revealed distinct temporal patterns between 2D monolayer cultures and 3D spheroids. In the 3D system, LC3B-II levels progressively increased, accompanied by a reduction in p62, suggesting altered regulation of autophagic flux relative to conventional 2D conditions. These findings demonstrate that the RADA16-I-based 3D culture model supports prolonged HSV-1 infection and reproduces key spatial features of viral dissemination. The differential autophagic responses observed between 2D and 3D systems highlight the influence of cellular architecture on host–virus interactions and support the application of 3D culture platforms for mechanistic studies of HSV-1 pathogenesis. Full article

Zika virus (ZIKV), a unique flavivirus with neurotropic and teratogenic potential, can cross the blood–brain barrier and persist in human brain microvascular endothelial cells (BMECs); however, no approved vaccines or specific antivirals exist, and its barrier-crossing and neuroinvasive mechanisms remain elusive. Innovative strategies to identify additional host factors mediating ZIKV infection could yield key insights and help address these challenges. To uncover novel host factors, we established the first tree shrew (Tupaia belangeri) genome-wide CRISPR/Cas9 knockout (GeCKO) library and performed a screen in BMECs, identifying ring finger protein 6 (RNF6) as a novel proviral factor for ZIKV. ZIKV infection in BMECs was significantly reduced following RNF6 knockout or knockdown but enhanced upon RNF6 overexpression or rescue. Mechanistically, RNF6 interacts with the ZIKV NS5 protein and acts as a potential negative regulator of the type I interferon and MAPK signaling pathways. Evolutionary and structural analyses revealed that RNF6 is highly conserved between humans and tree shrews; molecular docking further identified shared NS5-binding residues (Gln-59, Arg-140), supporting the conserved proviral role of human RNF6 in ZIKV infection. Our findings highlight tree shrew GeCKO screening as an efficient approach for identifying novel host factors and establish RNF6 as a critical proviral factor for ZIKV replication in BMECs, providing new insights into ZIKV neurotropic pathogenesis and informing potential antiviral strategies. Full article

Background/Objectives: Miller–Fisher syndrome (MFS) is a rare Guillain–Barré variant defined by ophthalmoplegia, ataxia, and areflexia. Pediatric MFS is uncommon, and infectious triggers remain underrecognized. Human herpesvirus 6 (HHV-6) is neurotropic but rarely linked to immune-mediated neuropathies. In this paper, we describe a child with MFS associated with HHV-6 detected in cerebrospinal fluid (CSF) and review reported pediatric infections related to MFS. Methods: A 5-year-old girl presented with acute ophthalmoplegia, ataxia, and diminished reflexes. Neuroimaging, ophthalmologic tests, CSF analyses, and serologic andpolymerase chain reaction (PCR) assays were performed, including multiplex reverse transcription–PCR of cerebrospinal fluid using the BioFire^® Meningitis/Encephalitis panel. A literature search was performed on Pubmed to identify pediatric (0–18 years) MFS cases with infectious triggers. Two reviewers independently screened and summarized the literature, and a PRISMA-style flow diagram was used to transparently report the study selection process. Results: HHV-6 DNA was detected via CSF PCR twice, while tests for other pathogens were negative. Anti-GQ1b and related antibodies were negative or borderline. The patient received intravenous immunoglobulin and corticosteroids, with full recovery after one month. Among 20 published pediatric cases (1997–2021), Campylobacter jejuni was most frequent, followed by Mycoplasma pneumoniae and influenza viruses. Anti-GQ1b IgM positivity and favorable outcomes were commonly reported, including cases managed conservatively. Conclusions: This case raises the hypothesis that HHV-6 may represent a potential post-infectious association in pediatric MFS. The review findings indicate that pediatric MFS generally follows infection, responds well to immunotherapy, and has an excellent prognosis. Viral testing may be considered in selected, hypothesis-generating contexts in atypical or seronegative pediatric MFS presentations. Full article

Coxsackievirus A16 (CVA16), a major etiological agent of hand, foot, and mouth disease, is increasingly contributing to neurological complications, with no vaccines or virus-specific antivirals currently available. To identify CVA16-restricting host factors, we investigated the role of the interferon-stimulated gene shiftless (SHFL), previously implicated in the control of other RNA viruses. Using CRISPR–Cas 9, we generated SHFL knockout rhabdomyosarcoma cells and assessed viral replication, cytopathic effects, and replication stage dynamics. We evaluated disease progression and tissue injury in neonatal mice infected with a mouse-adapted CVA16 strain. SHFL expression was strongly induced during CVA16 infection and was inducible by exogenous interferon-β treatment, and its loss markedly increased infectious virus production, accelerated early replication, and exerted severe cytopathic effects. In vivo, SHFL deficiency led to rapid weight loss, pronounced neurological signs, increased viral burden across multiple tissues, and uniform mortality, together with high viral loads and extensive pathological damage in the central nervous system, lungs, and skeletal muscle. Transcriptomic analyses revealed SHFL-dependent modulation of adhesion- and mitogen-activated protein kinase-related pathways. Overall, our results suggest SHFL as a key determinant of host resistance to CVA16, acting mainly at the post-transcriptional stage to limit viral spread and tissue injury, and highlight SHFL-linked pathways as promising host-directed antiviral targets. Full article

Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection patterns. This tropism shift coincided with microglial activation (allograft inflammatory factor 1, amoeboid transformation) and astrocytic activation (nestin), along with T-cell infiltration and endothelial activation that persisted beyond viral clearance. SPBNGAK-infected astrocytes expressed nestin, while GAS variant-infected astrocytes remained nestin-negative and were rapidly cleared. Intracerebral co-inoculation of astrocytotropic TriGAS with the lethal neurotropic DOG4 strain was associated with survival and a marked reduction in detectable DOG4 neuronal infection. These findings suggest that glycoprotein-mediated astrocyte tropism may be associated with altered immune responses after rabies CNS invasion. While mechanistic causality cannot be inferred, these observations may inform the design of future studies exploring astrocyte-restricted RABV infection in therapeutic-related contexts. Full article

Background: Bilateral facial nerve palsy (BFNP) is a rare clinical entity in children and is more often associated with systemic or infectious diseases than unilateral facial palsy. Epstein–Barr virus (EBV) infection is an uncommon but recognized cause of facial nerve palsy and may present with bilateral involvement. Case presentation: We report the case of a 3-year-old boy who presented with progressive bilateral facial weakness following a febrile illness with pharyngitis and cervical lymphadenopathy. Neurological examination revealed complete bilateral facial paralysis (House–Brackmann grade VI). Laboratory investigations showed lymphocytosis and confirmed acute EBV infection through positive viral capsid antigen IgM and detectable EBV DNA in peripheral blood. Cerebrospinal fluid analysis demonstrated mild pleocytosis with negative EBV DNA. Brain magnetic resonance imaging revealed unilateral enhancement of the left facial nerve. Audiologic evaluation supported peripheral facial nerve dysfunction. The patient was treated with systemic corticosteroids, vitamin B complex supplementation, artificial tears, and speech therapy, resulting in gradual and substantial clinical improvement over five months. Discussion: A review of the pediatric literature identified only six previously reported cases of EBV-associated BFNP. The pathogenesis may involve either direct viral neurotropism or a post-infectious immune-mediated mechanism. Diagnostic evaluation is essential to exclude other serious causes of BFNP, particularly Lyme disease and Guillain–Barré syndrome. Conclusions: EBV infection should be considered in the differential diagnosis of BFNP in children. Prognosis is generally favorable, although recovery may be prolonged. Further studies are needed to clarify optimal diagnostic and therapeutic approaches. Full article

Exposure to lead is associated with microglial dysfunction and the development of neuroinflammation. This contributes to accelerated neurodegeneration. Even low doses of this element modulate inflammatory responses and might contribute to central nervous system dysfunction. Extracts from the mushroom Hericium erinaceus (HE) possess well-documented neurotropic properties; however, its potential neuroprotective mechanisms under conditions of environmental neurotoxicity remain poorly defined. In this study, we investigated the effects of HE on inflammatory signaling in a microglia-oriented in vitro model using THP-1-derived macrophages exposed to low levels of lead (3.5 µg/dL). In our study, Pb exposure did not increase tumor necrosis factor (TNF) alpha levels but reduced monocyte chemoattractant protein-1 (MCP-1) secretion and altered cyclooxygenase (COX) expression, indicating immune response modulation rather than inflammatory activation. Under combined Pb and HE exposure, a marked shift in cyclooxygenase expression toward COX-2 at both the gene and protein levels was observed, accompanied by increased PGE₂ production; these effects were dose-dependent. The inflammatory signaling was modulated rather than amplified. Also, TNF alpha levels were elevated after combined treatment, whereas gene expression responses were dose-dependent. MCP-1 secretion was fine-tuned toward control values, consistent with macrophage morphological changes, while IL-6 levels were increased. Overall, these findings indicate that Hericium erinaceus exerts immunomodulatory effects in microglia-like cells under low-level lead exposure, supporting its neuroprotective potential through modulation of neuroinflammatory signaling. Full article