Chikungunya virus (CHIKV) infection is typically not life threatening but may, in rare cases, affect the central nervous system (CNS). In three cohorts of confirmed CHIKV cases from Martinique (French overseas territory) and Brazil (patients aged 0 to 89 y, n = 245), 20 patients had CNS infection (aged 17 to 87 y). Autoantibodies neutralizing type I interferons (AAN-I-IFN) were found in 35% of patients (4 male and 3 female, aged 17 to 87 y) with encephalitis (4/15), encephalomyelitis (1/2), or myelitis (2/3), but were absent in 225 patients without CNS infection. They neutralized high concentrations (10 to 1,000 ng/mL) of IFN-α2, IFN-α8, and IFN-ω, and the antibodies of one patient also neutralized IFN-β. All samples also neutralized the other 10 IFN-α subtypes (at least 100 pg/mL). This combination of blood autoantibodies occurs in ~0.02% and 0.6% of healthy individuals under and over 70 y of age, respectively. The presence of AAN-I-IFN before CHIKV infection therefore increased the risk of CNS disease ~850-fold relative to the general population.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus transmitted by a wide range of mosquito vectors present across the African continent. RVFV has resulted in large-scale epidemics in East, West, southern, and northern Africa with additional epidemics affecting the Arabian Peninsula, Mayotte, and Comoros. In some areas, rather than large-scale isolated outbreaks, RVFV causes a fluctuating low-level endemic burden affecting livestock populations by resulting in pregnancy loss and significant production losses. RVFV risk extends into the human population when it is transmitted either by vector-borne transmission or direct contact with infected animals or animal products such as blood, meat, or milk. Following infection, 2%-3% of humans can develop severe disease manifestations including encephalitis/meningitis, hemorrhagic fever, and retinitis, with visual deficits commonly reported among survivors. While RVF cases in animals and humans have been spatially linked, the proportion and risk associated with spillover events is poorly classified. Given RVFV's dual threat to human and livestock health, it has been designated a priority pathogen by WHO for development of countermeasures. This review aims to summarize current knowledge of RVFV epidemiology, infection, and control as well as highlight key recent advances in the understanding of epidemiology and vaccine development. Multiple next-generation vaccine candidates have advanced to phase two clinical trials which offer hope for approved and commercially available human vaccines in the coming decades. However, despite these promising advancements, key gaps in knowledge remain, particularly regarding the total burden and geographic distributions of endemic and epidemic infections, shifting epidemiologic patterns, optimal vaccine use cases, and the effects of RVFV infection on pregnancy in humans living in hyperendemic regions. Many gaps in understanding persist, and RVFV remains a quintessential One Health pathogen requiring coordinated human, animal, and environmental investigation and collaboration to translate scientific advances into effective national public health strategies.

Neurotropic coronaviruses can invade the central nervous system (CNS) and cause severe neurological disease, but the mechanisms underlying virus-induced neuroinflammation remain incompletely understood. Here, we report that infection with porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, is associated with mitochondrial dysfunction, including increased reactive oxygen species (ROS) production and loss of the mitochondrial membrane potential (ΔΨm). Our data identify the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome as an important component connecting PHEV infection, mitochondrial stress, and PANoptosis. The viral nucleocapsid (N) protein interacted with the pyrin domain (PYD) of NLRP3 through its C-terminal region and facilitated inflammasome assembly without detectably disrupting the NLRP3-NIMA-related kinase 7 (NEK7) interaction. Pharmacological inhibition of NLRP3 or caspase-1, as well as genetic knockout of NLRP3, significantly reduced viral load, attenuated neuroinflammation, and delayed disease progression in PHEV-infected mice. Moreover, NLRP3 deficiency shifted the cell-death modality from PANoptosis to necroptosis, thereby mitigating CNS immunopathology. Together, these findings demonstrate that PHEV hijacks the NLRP3-mitochondrial axis to exacerbate neuroinflammatory injury and support further evaluation of inflammasome- and PANoptosis-related pathways as therapeutic targets for neurotropic coronavirus infections.IMPORTANCEPorcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic betacoronavirus that primarily invades the central nervous system (CNS) and induces fatal encephalomyelitis in young piglets. However, the host and viral determinants that contribute to PHEV-induced brain injury remain incompletely defined. In this paper, we show that PHEV infection activates the host NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway and that this response contributes to CNS immunopathology. Loss of NLRP3 shifts the infection-associated cell death program from PANoptosis to necroptosis. Blocking this pathway reduces viral load, attenuates neuroinflammation, and improves survival in infected mice. These findings expand our understanding of host responses to neuroinvasive coronaviruses and highlight inflammasome signaling as a candidate therapeutic target for controlling coronavirus-associated encephalitis in swine.

Nipah virus (NiV) is a high-consequence zoonotic henipavirus characterised by severe encephalitis and respiratory distress, driving recurrent outbreaks with case fatality rates between 40% and 75% in India and Bangladesh. Within these outbreaks, 'super-spreading' dynamics play a critical role, where a small subset of individuals contributes to a disproportionately large share of secondary infections. To evaluate the relationship between human infectivity and viral load kinetics in Nipah virus infection and to define the role of the medical laboratory in identifying potential super-spreaders, a narrative review was conducted by executing a systematic search across PubMed, Scopus, and ScienceDirect for peer-reviewed literature published from 1998 to 2025. The qualitative synthesis demonstrated that NiV infectivity is highly dependent on specimen matrix efficiency and anatomical shedding patterns. Respiratory specimens yield the highest viral RNA copy numbers during the acute symptomatic phase, correlating strongly with active droplet transmission. Persistent real-time RT-PCR Cycle Threshold values below 25 (Ct < 25) in respiratory samples serve as an indirect laboratory indicator of high-risk shedders and should be interpreted alongside clinical and epidemiological findings. However, a comprehensive analysis indicates that super-spreading is inherently multifactorial. Early identification via frontline molecular diagnostics remains the cornerstone of breaking NiV transmission chains. Although a standalone viral load threshold is insufficient to predict a spreading event on its own, the medical laboratory provides an essential risk profile by combining longitudinal Ct kinetics with clinical and exposure data. Strengthening regional laboratory infrastructure and deploying standardized point-of-care molecular assays in endemic, resource-limited areas are urgent public health priorities.

Tuberculous meningitis (TBM) typically presents with infection-related symptoms and biomarkers. We report a diagnostically challenging case of a 63-year-old woman with newly diagnosed diabetes who presented with stroke-like onset (hemiparesis, aphasia) but completely lacked typical infectious symptoms and signs. Neuroimaging features and near-normal cerebrospinal fluid (CSF) initially pointed to viral encephalitis, and complete resolution of symptoms following empirical treatment for viral encephalitis further confounded the diagnosis, as did coexisting venous anomalies. Notably, despite no recurrence of symptoms after treatment withdrawal, follow-up brain MRI revealed paradoxical progression of the lesions. All microbiological tests, including GeneXpert and next-generation sequencing (NGS), remained negative until meningeal biopsy demonstrated granulomatous inflammation with a single acid-fast bacillus and a positive interferon-gamma release assay (IGRA). This case underscores that TBM can masquerade as stroke, encephalitis, or non-infectious conditions, reinforcing the need for high clinical suspicion and, when indicated, tissue biopsy to establish a highly probable diagnosis.

HSV-1 encephalitis (HSE) remains a devastating viral infection of the central nervous system despite effective antiviral therapy. Increasing evidence indicates that disease outcome is not determined by viral replication alone but by how innate immunity is calibrated within the brain. Studies of host susceptibility in childhood HSE have identified brain-intrinsic antiviral mechanisms, referring to central nervous system (CNS)-localized innate immune pathways that enable resident brain cells to sense and restrict HSV-1 infection, particularly TLR-dependent interferon responses, neuron-associated restriction factors, and other CNS-resident innate immune mechanisms. Host innate immune responses initially contribute to viral restriction, whereas excessive or unresolved activation can promote inflammatory amplification and long-term neurological injury. In parallel, HSV-1-mediated immune remodeling may weaken antiviral control and alter the subsequent inflammatory trajectory. Here, HSE is discussed as a dynamic immunopathological disorder in which protective innate immunity can transition into pathogenic neuroinflammation. Building upon these observations, we propose that host-directed therapeutic strategies should shift from uniform immune modulation toward stage-specific immune recalibration on the basis of viral control, antiviral competence, inflammatory persistence, and tissue repair.

Dengue virus, an arthropod-borne pathogen, poses a significant global public health concern, necessitating the development of sensitive and rapid diagnostic assays. This paper introduces a novel biosensing platform designed for the ultrasensitive detection of dengue viral RNA. The platform integrates recombinase polymerase amplification, CRISPR/Cas13a-based recognition, and electrochemiluminescence resonance energy transfer (ECL-RET). The sensor employs a highly efficient luminescent emitter, which is a ternary composite of gold-platinum nanoparticles supported on graphitic carbon nitride and graphene oxide. A suitable energy acceptor, consisting of silver-decorated metal-organic frameworks, effectively quenches the emitter's signal via resonance energy transfer. Upon the introduction of target nucleic acids, RPA rapidly generates numerous amplicons. These amplicons are specifically recognized by the CRISPR/Cas13a system, which subsequently activates the collateral cleavage activity of Cas13a. This enzymatic activity cleaves a DNA linker that tethers the acceptor to the electrode surface, leading to the release of the acceptor and a subsequent restoration of the electrochemiluminescence intensity. The recovered signal exhibits a linear proportionality to the target concentration across a broad dynamic range, spanning from 0.1 fg/mL to 100 ng/mL. The detection limits for the four dengue serotypes range from 1.09 to 2.5 fg/mL. The assay demonstrates excellent specificity, showing no cross-reactivity with Zika, Japanese encephalitis, or West Nile viruses, and also exhibits good reproducibility. By combining isothermal amplification, specific CRISPR targeting, and a sensitive luminescence readout, this work presents a straightforward and robust method for the early diagnosis of dengue and for outbreak surveillance. Furthermore, this platform can be readily adapted for the detection of other pathogens of interest.

Nipah virus (NiV) is a zoonotic, highly pathogenic, negative-sense RNA virus belonging to the genus Henipavirus (family Paramyxoviridae), causing severe encephalitis and/or acute respiratory illness in humans. Reported outbreaks show case-fatality rates ranging from approximately 40- 90%, influenced by healthcare quality, surveillance capacity, and clinical variability. Fruit bats (Pteropus spp.) serve as the natural reservoir, with transmission to humans occurring directly or through intermediate hosts such as pigs. Multiple outbreaks have confirmed efficient human-to-human spread, especially in healthcare and household settings. NiV's broad host range, high virulence, and absence of approved therapeutics or vaccines justify its classification as a World Health Organization (WHO) priority pathogen with pandemic potential. Current vaccine candidates-including glycoprotein subunits, viral vectors, virus-like particles, and mRNA platforms-target the viral attachment (G) and fusion (F) glycoproteins. Advancing NiV prevention demands a One Health approach integrating ecology, livestock management, community education, and robust clinical evaluation.

To investigate alterations in the amplitude of low-frequency fluctuations (ALFF) in herpes simplex encephalitis (HSE) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and evaluate their associations with anxiety symptoms. In this single-center cohort study, 45 HSE patients and 46 healthy controls (HC) were recruited from the First Affiliated Hospital of Zhejiang University School of Medicine, China. HSE was confirmed by clinical features and positive herpes simplex virus (HSV) DNA in cerebrospinal fluid via polymerase chain reaction. Participants underwent rs-fMRI scans within one week of ICU admission. ALFF was calculated using REST software; group differences were assessed with voxel-wise two-sample t-tests (covariates: age, sex, education, framewise displacement; whole-brain voxel-wise FDR-corrected P < 0.05) and validated nonparametrically. Associations between ALFF and anxiety (Hamilton Anxiety Rating Scale, HAMA) were examined via general linear models, controlling for age, sex, hypertension, and education, with Spearman's correlations for robustness. Compared to HC, HSE patients exhibited increased ALFF in the left precuneus and right putamen, alongside decreased ALFF in the right angular gyrus and right caudate nucleus (whole-brain voxel-wise FDR-corrected P < 0.05). These changes correlated significantly with HAMA scores: positive associations in hyperactive regions (left precuneus: β = 0.558, 95% CI: 0.312 to 0.805, p < 0.001; right putamen: β = 0.511, 95% CI: 0.254 to 0.768, p < 0.001) and negative associations in hypoactive regions (right angular gyrus: β = -0.517, 95% CI: -0.773 to -0.261, p < 0.001; right caudate: β = -0.556, 95% CI: -0.804 to -0.307, p < 0.001). No significant correlations emerged with depression scores (Hamilton Depression Rating Scale). HSE induces region-specific ALFF disruptions, characterized by hyperactivity in the precuneus and putamen together with hypoactivity in the angular gyrus and caudate within limbic-paralimbic networks. These alterations show strong associations with anxiety severity, suggesting ALFF as a potential noninvasive biomarker for HSE-related functional and neuropsychiatric impairments. Larger longitudinal studies are warranted to elucidate underlying mechanisms and therapeutic implications.

We report the detection of tick-borne encephalitis virus (TBEV) in Dermacentor reticulatus ticks collected in Poland during the 2022 season. Both Ixodes ricinus and D. reticulatus ticks were surveilled. There was limited TBEV detection found in one pool out of 106 pools (418 ticks) that were shotgun genome sequenced. The TBEV positive tick pool consisted of N = 3 adult D. reticulatus ticks. Additional hybrid-capture sequencing of this pool resulted in the first full-length genome sequence of TBEV from this tick species. The assembled genome was classified as the European subtype through phylogenetic analysis. The new TBEV sequence is phylogenetically placed closest to a 2019 Hungarian isolate, suggesting potential viral migration or shared ancestry across nearly 1,000 km. These findings expand the known geographic range of TBEV circulation in Poland and highlight the role of D. reticulatus as an important vector of TBEV.

Anti-John Cunningham virus (JCV) serological testing constitutes a cornerstone of progressive multifocal leukoencephalopathy (PML) risk assessment in patients receiving natalizumab for multiple sclerosis (MS). Existing PML risk stratification algorithms were originally developed and validated within a single-assay framework based on the STRATIFY JCV™ DxSelect™ platform. The recent introduction of natalizumab biosimilars in Europe has coincided with implementation of IMMUNOWELL™ JCV IgG assay, creating a multi-assay environment in which quantitative antibody index values and binary serostatus classifications may not be directly interchangeable. We conducted a structured narrative review of comparative studies evaluating STRATIFY and IMMUNOWELL performance in natalizumab-treated cohorts. Outcomes included seroprevalence, qualitative concordance, quantitative index distribution, reclassification across established PML risk categories, and reported changes in clinical management. Across analytical validation datasets and real-world populations, IMMUNOWELL classified a higher proportion of individuals as JCV-positive than STRATIFY. Reported binary discordance ranged from approximately 6% to 38%, with a predominance of IMMUNOWELL-positive/STRATIFY-negative classifications. Longitudinal studies further showed that many low-positive IMMUNOWELL results fluctuated or reverted over time. The available evidence suggests that the transition from a mono-assay to a multi-assay testing environment introduces a previously underrecognized source of variability in PML risk stratification. In the absence of a biological gold standard for latent JCV infection, interpretation of discordant results should integrate antibody magnitude, longitudinal persistence, and clinical context rather than relying on binary thresholds.

Measles is a highly contagious viral disease whose incidence has declined significantly since the introduction of vaccination in the mid-1970s. However, local outbreaks continue to occur due to insufficient vaccination rates. Adults are at higher risk of complications. The present case of a patient with acute post-infectious measles encephalitis despite a history of presumed measles vaccination underscores the critical importance of vaccination as a preventive measure. In everyday general practice, there is an opportunity to identify individuals who have not been vaccinated against measles and to guide them toward achieving full vaccination coverage.

Neurotropic viruses can alter neuronal responses in the central nervous system (CNS), significantly affecting viral clearance and disease progression. Herpes simplex virus type 1 (HSV-1) brain infection may lead to life-threatening severe acute encephalitis in untreated patients and neurological sequelae in survivors despite antiviral treatment. Notably, asymptomatic brain infection occurs in an important proportion of healthy individuals (>35%) and is associated with residual chronic neuroinflammatory responses that may lead to neurodegeneration. Therefore, understanding the molecular basis of these detrimental effects and finding and advancing new therapeutic strategies to manage HSV-1 brain infections are needed. Neuropeptides are pleiotropic neuroimmune mediators expressed throughout the CNS that modulate glial activation, cytokine production, and neuronal survival. However, their regulation during HSV-1 brain infections remains largely unexplored. Here, we sought to investigate the expression dynamics of two neuropeptides, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), in two mouse strains that model human traits of symptomatic and asymptomatic HSV-1 brain infections (BALB/c and C57BL/6, respectively), as well as in the human neuroblastoma cell line SH-SY5Y, to uncover potential differences that could help explain the susceptibility of some individuals to develop severe HSV-1 infection. Our findings provide evidence that HSV-1 brain infection modulates NPY and VIP mRNA expression in a neurovirulence- and host-susceptibility-dependent manner, which may be associated with disease severity and chronic damage, warranting further evaluation.