Search Results (2,081)

Senecavirus A (SVA), an emerging causative agent of porcine vesicular disease, belongs to the genus Senecavirus of the family Picornaviridae. The virus has been circulating in pig herds in the USA dating back to 1988, evolved into clinically significant pathogenic SVA variants causing a pandemic in the USA and Canada since 2014, and thereafter gradually spread to the Americas and Asia. To date, most studies have illustrated the infection dynamics, epidemiology, diagnostic methods, and vaccine development, yet the molecular pathogenesis of SVA remains incompletely characterized. As a novel picornavirus capable of establishing persistent subclinical infections, SVA has been detected in tissues such as tonsils and testicles for up to 156 days post-infection, posing a substantial challenge to swine health and production systems. In parallel, SVA has gained attention as an oncolytic virotherapy candidate for neuroendocrine tumors due to its tumor-selective tropism. Therefore, elucidating the mechanisms underlying SVA pathogenesis will not only support the development of effective countermeasures for swine but also inform the engineering of recombinant variants with enhanced therapeutic potential for human oncology. This review comprehensively summarizes the current knowledge on viral and host determinants of SVA pathogenesis, from the viral genome, evolution, and recombination to ANTXR1 host immunity, and programmed cell death, and presents future research directions, aiming to identify key knowledge gaps to guide future studies on SVA. Full article

Hepatitis E virus (HEV) infection, once regarded as a self-limiting hepatic disease confined to endemic regions, is now recognized as a systemic condition with a broad spectrum of extrahepatic manifestations. Among these, neurological complications—including peripheral neuropathies such as Guillain–Barré syndrome and neuralgic amyotrophy, and central nervous system involvement such as meningitis, encephalitis, and meningoencephalitis—are the most clinically relevant. Meningoencephalitis, though less common, is the most severe and underdiagnosed neurological expression of HEV infection. This narrative review examines current evidence on HEV-associated meningoencephalitis, covering epidemiology, pathogenesis, clinical features, and therapeutic strategies. Neurological disease is dominated by genotype 3 and frequently anicteric, with symptoms preceding or masking hepatic involvement. Pathogenesis is multifactorial, combining direct viral neurotropism—supported by HEV RNA detection in cerebrospinal fluid and replication in induced pluripotent stem cell (iPSC)-derived neurons and brain organoids—with immune-mediated mechanisms such as molecular mimicry and microglia-driven neuroinflammation. Diagnosis is often delayed by the absence of jaundice and low clinical suspicion, even though HEV remains an unrecognized cause in many unexplained encephalitis cases in high-income settings. Ribavirin remains the antiviral mainstay, but viral persistence within CNS sanctuary sites raises concerns about treatment adequacy and relapse; emerging antiviral and immunomodulatory strategies remain under investigation. HEV should be systematically considered in the diagnostic workup of unexplained neurological syndromes, regardless of overt hepatitis; heightened clinical awareness remains the most immediately actionable step toward reducing the burden of this still under-recognized condition. Full article

Background/Objectives: Celiac disease (CeD) is a complex autoimmune enteropathy triggered by gluten intake in genetically predisposed individuals. While the bacterial microbiome has been extensively studied in CeD, the role of the gut virome and mycobiome is less well defined. Emerging evidence suggests that viruses and fungi may influence mucosal immunity, intestinal permeability and gluten tolerance, acting as potential environmental cofactors in the onset of this disease. Methods: A narrative review of the literature was conducted to summarize current knowledge of the composition, development and function of the gut virome and mycobiome and to explore their potential involvement in CeD pathogenesis. Results: The gut virome shows high interindividual variability and dynamic maturation early in life. Multiple studies have associated early enterovirus or parechovirus infections with an increased risk of celiac autoimmunity, supporting a virus–gluten “double hit” model. Viral dysbiosis in CeD has been reported to include an enrichment of human polyomavirus 2 (JC polyomavirus) and of specific enterobacterial phages. The mycobiome, although less abundant, also displays disease-associated alterations: cross-sectional mycobiome studies have reported higher relative abundance of Saccharomyces, Candida, and Tricholomataceae and lower relative abundance of Pichia and Pneumocystis taxa in children with CeD. Conclusions: Current evidence, although preliminary, supports associations between selected viral exposures and CeD-related immune alterations, whereas current phageome and mycobiome findings mainly describe cross-sectional compositional differences. These data do not establish temporal direction or causality, and further longitudinal and mechanistic investigations are required before preventive or therapeutic implications can be considered. Full article

Highly pathogenic RNA viruses, such as Ebola, SARS-CoV-2, and influenza, cause severe disease in humans. High mutation rates, which enable RNA viruses to evade immunity and escape antivirals, and their ability to spread from animals to humans and cause pandemics and outbreaks, make RNA viruses significant threats to public health. Diseases caused by Ebola, SARS-CoV-2, and influenza are prevented and treated with only a limited number of approved antiviral drugs, the effectiveness of which is limited by mutations in the viral targets. It is crucial to understand the structural determinants, molecular mechanisms, and host interactions of pathogenic RNA viruses to develop effective antiviral strategies. In this review, we discuss selected RNA viruses, focusing on the structure of their RNA polymerases and interactions with host factors during the different stages of the viral lifecycle, as well as the traditional antivirals targeting these structures and pathways. Furthermore, emerging concepts such as liquid–liquid phase separation and biomolecular condensates, and novel promising antiviral strategies are discussed. Understanding shared and distinct structures, molecular mechanisms, and host interactions across highly pathogenic RNA viruses enables the discovery of new and more effective antiviral strategies, ultimately improving clinical outcomes against evolving RNA viruses. Full article

Feline kobuvirus (FKoV) has been linked to diarrheal disease in cats and has recently emerged in several Asian countries. This study aimed to investigate the epidemiological and genetic characterization of FKoV in domestic cats in northern Vietnam from 2022 to 2025. In total, 244 fecal samples were obtained from both healthy and sick cats in Hanoi, Hungyen, Bacninh, and Ninhbinh in the north of Vietnam. Of 244 fecal samples examined, eight (3.28%) samples were found to be positive for the FKoV genome by using the conventional PCR method. Viral genomes were identified in both healthy and sick cats. The highest FKoV-positive rate was 12.50% in 6–12-month-old cats, significantly higher than those detected in cats aged 3–6 months and >12 months. Eight positive samples were successfully sequenced and characterized for the partial 3D gene and full-length VP1 genes. Results showed that the level of nucleotide identity of the partial 3D gene and full-length VP1 genes among the FKoV strains in this study ranged from 95.86% to 100% and 94.09% to 99.73%, respectively. Phylogenetic analysis revealed that the eight Vietnamese viral strains obtained in this study formed a novel cluster within FKoV and are genetically related to Chinese FKoV strains. Two positive selections were found in the VP1 protein of the Vietnamese FKoV strains. Full article

Dementia with Lewy bodies (DLB) is increasingly conceptualised not merely as a disorder of neuronal death but as a primary synaptopathy in which the functional collapse of synaptic transmission and plasticity precedes, and predicts, neurodegeneration and clinical decline. Two genetic determinants dominate the heritable risk architecture of DLB: the α-synuclein gene SNCA, in which both copy-number variation and missense mutations exert dose- and conformation-dependent effects, and GBA1, encoding the lysosomal hydrolase glucocerebrosidase (GCase), the single most influential genetic risk factor for the disease. Here we synthesise evidence that these loci converge on a shared pathogenic endpoint—the impairment of activity-dependent synaptic plasticity. We argue that GBA1 loss-of-function and the resulting accumulation of glucosylceramide stabilise specific neurotoxic α-synuclein proteoforms, including soluble oligomers and self-templating conformational strains bearing defined post-translational modifications. These proteoforms are trafficked to, and enriched within, presynaptic terminals, where they disrupt SNARE-complex assembly and synaptic-vesicle dynamics, while postsynaptically they perturb NMDA and AMPA receptor trafficking, dysregulate dendritic calcium, and compromise synaptic mitochondrial bioenergetics. The net consequence is a metaplastic shift away from long-term potentiation (LTP) and toward aberrant long-term depression (LTD), a signature of synaptic failure detectable before frank pathology. We map these molecular events onto disease-relevant circuits—particularly the cholinergic basal forebrain and hippocampal–cortical and thalamocortical networks—and relate them to the defining neuropsychiatric features of DLB, including cognitive fluctuations and recurrent visual hallucinations. Finally, we evaluate emerging therapeutic strategies that target the GBA1–α-synuclein axis and that aim to restore synaptic plasticity directly. Positioning DLB within the framework of genetically determined plasticity deficits clarifies its kinship with other neuropsychiatric disorders and identifies the synapse as the most tractable node for early, disease-modifying intervention. We further examine how GBA1 allele severity and zygosity grade the phenotype, which genetic and environmental factors modify penetrance in carriers, and what distinguishes this synaptopathy from those driven by PSEN1/PSEN2, MAPT, or HTT, and we summarise the therapeutic pipeline—including enzyme augmentation and adeno-associated viral GBA1 gene therapy—that targets it. Full article

Sweet potato (Ipomoea batatas (L.) Lam) is an important global food crop, but its production is threatened by numerous viral pathogens. More than 30 RNA and DNA viruses have been reported worldwide, making rapid and accurate detection essential for disease management, epidemiological surveillance, germplasm exchange, and resistance breeding. Although previous reviews have addressed sweet potato viruses and individual diagnostic methods, a comprehensive synthesis of emerging molecular technologies remains limited. This review addresses that gap by critically integrating recent advances from PCR-based and isothermal assays to high-throughput sequencing, CRISPR-based diagnostics, biosensors, nanotechnology, and artificial intelligence-driven detection platforms. Conventional approaches, including symptom observation, biological indexing, electron microscopy, and ELISA, have contributed to early virus identification but often lack the sensitivity, specificity, and speed needed for modern diagnostics. Molecular and isothermal techniques have substantially improved detection accuracy and enabled rapid identification and field-deployable diagnostics of diverse and mixed infections, while sequencing, CRISPR, biosensors, and AI-based platforms offer greater capacity for detecting novel and emerging viruses. This review discusses the comparative evaluation of molecular technologies for sweet potato virus detection in terms of diagnostic performance, cost-effectiveness, speed, and suitability for both laboratory and field applications, while highlighting future priorities for next-generation virus diagnostics. Integrating portable and high-throughput diagnostic platforms will strengthen virus surveillance, support virus-free planting material production, and promote sustainable sweet potato production worldwide. Full article

Background/Objectives: The blood–brain barrier (BBB) remains a major obstacle to effective gene therapy for neurological disorders by limiting delivery of viral vectors, nanoparticles, and biologics to the central nervous system. Multiple strategies have been developed to transiently disrupt or bypass the BBB, including focused ultrasound (FUS) with microbubbles, osmotic agents, biochemical modulators, and receptor-mediated transport systems. Among these approaches, FUS-mediated BBB opening has emerged as the most spatially precise and clinically advanced strategy. Methods: This narrative review synthesizes recent preclinical and clinical literature on BBB microdisruption technologies for central nervous system gene therapy, with primary emphasis on FUS combined with microbubbles. We review BBB physiology, gene delivery platforms, the development of FUS technologies, optimization parameters, and translational evidence across neurological diseases from animal models through early-phase human studies. Results: FUS-mediated BBB opening has emerged as the leading method for transient barrier modulation. Preclinical studies in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, glioblastoma, amyotrophic lateral sclerosis, and lysosomal storage disorders demonstrate enhanced gene delivery, increased transgene expression, and improved functional outcomes. Large-animal studies and early clinical trials indicate that BBB opening is reversible, spatially controlled, and generally well tolerated. Clinical investigations have demonstrated successful delivery of therapeutic agents across neurological indications, with preliminary efficacy signals including improved drug penetration, metabolic changes, and potential survival benefits. Optimization of acoustic parameters, microbubble characteristics, and real-time cavitation monitoring remains critical for maximizing safety and therapeutic efficacy. Conclusions: BBB microdisruption, particularly through FUS with microbubbles, represents a transformative platform for central nervous system gene therapy. Continued research is needed to standardize treatment protocols, characterize long-term safety, and facilitate broader clinical translation. Full article

Enterovirus D68 (EV-D68) is a re-emerging pathogen associated with severe acute flaccid myelitis (AFM) and pneumonia, predominantly in children but also capable of causing severe disease in immunocompromised adults. Seroprevalence data are essential for understanding population immunity, age-specific susceptibility, and viral transmission dynamics; yet, such data for the period after the COVID-19 pandemic are scarce. We conducted a cross-sectional serological survey to characterize the neutralizing antibody profile of EV-D68 among children in Xiamen, China, in 2022. A total of 453 children aged 0–16 years (217 with acute respiratory tract infection [ARTI] and 236 without) were enrolled. Neutralizing antibody (NtAb) titers against the EV-D68 STL strain were measured using a microneutralization assay, seropositivity was defined as a titer ≥1:16. Multivariable regression and analysis of covariance were used to adjust for age and sex. Overall seroprevalence was 96.0% (435/453), exceeding 90.0% in every age subgroup (0–1 y: 100%; 1–3 y: 97.6%; 3–5 y: 92.6%; ≥5 y: 96.2%). The geometric mean titer (GMT) was 76.78 (95% CI: 68.32–85.24). After adjustment, ARTI status was not significantly associated with seropositivity (adjusted OR = 1.42, 95% CI: 0.46–4.41, p = 0.542). In an exploratory comparison, children with ARTI showed nominally higher antibody titers than those without (Mann–Whitney U test, p = 0.003), although the absence of EV-D68-specific PCR testing precludes etiologic attribution of respiratory symptoms to EV-D68 infection. Infants < 1 year showed the highest GMT (86.31), while children aged 1–3 years had the lowest GMT (63.52) and the largest low-titer fraction, indicating a susceptibility gap. Our study revealed EV-D68 circulated endemically in this pediatric population, establishing a high population immune baseline (>90.0%) with distinct age-dependent patterns. These findings provide key reference data for ongoing serosurveillance, outbreak risk assessment, and the evaluation of future vaccines or immunoprophylactic strategies should they become available. Full article

The geographic range and outbreak intensity of vector-borne viral infections are increasing as climate, land use, urbanization, and human mobility reshape vector ecology and human exposure. Despite their growing importance to public health, effective antiviral and preventive options remain limited for many emerging and reemerging vector-borne viruses due to viral genetic diversity, rapid evolutionary capacity, sporadic outbreak patterns, and economic constraints. While these viruses differ in taxonomy, genome organization, vector specificity, tissue tropism, and clinical manifestations, they exploit a shared vulnerability in host antiviral defense, particularly the timing of innate antiviral immunity to support viral replication, immune evasion, inflammatory dysregulation, and disease progression. Rather than simply suppressing antiviral defense, vector-borne viruses can delay early viral nucleic acid sensing, attenuate interferon induction or responsiveness, and extend the initial phase for viral replication. As viral burden increases and infected tissues undergo stress or damage, delayed immune activation can shift toward excessive inflammatory amplification, contributing to disease-specific pathology. In this study, we examine this temporal rewiring of innate antiviral immunity in representative vector-borne viruses such as dengue virus, chikungunya virus, and severe fever with thrombocytopenia syndrome virus and propose that understanding these conserved host dependencies may lead to broader, stage-specific, adaptable antiviral strategies that complement conventional virus-directed approaches. Full article

African swine fever (ASF) is a viral disease of domestic and wild pigs that has re-emerged as a major transboundary disease. Modelling using mechanistic, statistical, and machine learning (ML) approaches plays a key role in understanding ASF transmission and informing disease control, but the literature remains fragmented. To synthesise global ASF modelling efforts, we systematically reviewed studies applying these three approaches. We examined temporal and geographic trends, modelling objectives, explanatory variables, and model evaluation practices. A total of 151 papers published through 2024 met the inclusion criteria. Mechanistic (54.3%) and statistical (40.4%) approaches predominated, whereas ML (9.3%) was increasingly applied in recent years. Mechanistic models were primarily used to assess control strategies (48.8%) and transmission drivers (41.5%), statistical models to identify risk factors (63.9%) and spatiotemporal spread (32.8%), and ML for environmental suitability modelling (64.3%). Most were published from 2011 (99.3%) and focused on Europe (43.0%) and Asia (26.5%). Model evaluation remained inconsistent, with mechanistic papers frequently lacking model output uncertainty quantification (47.0%) and statistical papers often omitting model adequacy assessment (49.2%) and assumption checking (50.8%). Overall, ASF modelling approaches have developed complementary methodological roles, while geographic underrepresentation, limited representation of some transmission pathways, and inconsistent model evaluation remain important gaps. Full article

Background/Objectives: Neuroinflammation is increasingly recognized as a key mechanism linking infectious diseases with psychiatric disorders through interactions between peripheral immune activation, metabolic pathways, and brain network alterations. This review aimed to synthesize current evidence on the neuroimmune mechanisms and biomarkers underlying infection-associated psychiatric disorders. Methods: A narrative literature review structured according to the SANRA (Scale for the Assessment of Narrative Review Articles) criteria was conducted using the Web of Science Core Collection, PubMed/MEDLINE, Scopus and PsycINFO databases. Boolean search strategies identified studies investigating neuroinflammatory biomarkers, neuroimmune mechanisms, and psychiatric outcomes associated with infectious diseases. The search (January 2022–30 June 2026) included 76 studies in the final qualitative analyses. Results: The reviewed evidence consistently identified inflammatory cytokines and chemokines, complement proteins, blood–brain barrier markers, glial activation biomarkers, neuroaxonal injury markers, kynurenine pathway metabolites, neurotrophic factors, and neuroimaging markers as complementary indicators of infection-induced neuroimmune dysfunction. Across diverse bacterial, viral, parasitic, and systemic infections, these mechanisms converged on peripheral immune activation, blood–brain barrier disruption, microglial activation, kynurenine pathway dysregulation, impaired neurotrophic signaling, synaptic dysfunction, and altered brain network connectivity, contributing to depression, anxiety, psychosis, cognitive impairment, and fatigue. Based on these findings, a unified neuroimmune model integrating peripheral and central mechanisms is proposed. Conclusions: Neuroinflammation emerges as a shared biological pathway linking infections with transdiagnostic psychiatric phenotypes. Although no single biomarker currently demonstrates sufficient diagnostic specificity, integrated multimodal biomarker panels may improve biological stratification, facilitate earlier identification of high-risk patients, and support the development of mechanism-based precision approaches—including candidate anti-inflammatory pharmacological strategies currently under clinical investigation—for infection-associated psychiatric disorders. Full article

Human papillomavirus (HPV) infection is a necessary but insufficient cause of cervical cancer (CC) and reflects a long-standing host–virus equilibrium shaped by immune control, viral persistence, and latency. The transition from cytology-based screening to primary high-risk HPV testing has substantially improved early detection of cervical precancerous lesions but has also introduced new clinical challenges related to fluctuating test results, overdiagnosis, overtreatment, and patient anxiety, whose magnitude may vary across countries depending on screening organization and access to prevention services. This narrative review provides a clinically oriented overview of HPV-based CC screening in the context of evolving knowledge on HPV natural history, persistence, and immune interaction, and discusses the implications for the interpretation of test results and risk stratification. New emerging screening and triage approaches, including molecular biomarkers, exosome-based biomarkers, and artificial-intelligence-supported risk assessment, are reshaping CC prevention strategies by enabling more precise identification of women at risk for clinically significant disease. These tools may be particularly relevant in self-sampling-based screening pathways, where molecular triage strategies can reduce the need for additional clinician-collected samples and improve management of HPV-positive women. At the same time, improved understanding of viral latency and host-related determinants of progression supports a shift from binary test interpretation toward longitudinal and individualized risk assessment. Integrating biological insight with technological innovation may facilitate personalized screening strategies that maintain high sensitivity while reducing unnecessary interventions. An evolutionary-informed and risk-adapted approach to HPV-related disease management is essential to optimize prevention outcomes and preserve the benefits of population-based screening programs. Full article

The Ponto-Danubian Basin Acipenseridae family includes species of fish with high economic value, as well as some of the most vulnerable taxonomic groups in terms of biodiversity conservation worldwide. Viral diseases have been documented considerably less frequently than bacterial and parasitic diseases. However, the European sturgeon iridovirus (AcIV-E) and herpes viruses have recently emerged as epizootic pathogens, raising concerns about their potential impact on sturgeon populations in the Black Sea basin. Bacterial pathogens were the main cause of the diseases reported in the reviewed literature. Many of these pathogens belonged to the Genera Aeromonas, Vibrio, Pseudomonas, and Citrobacter. These pathogens were particularly implicated in the etiology of septicemic and hemorrhagic symptoms, which significantly impacted the mortality of affected populations. Ecto- and endoparasitic infestations were primarily caused by protozoa, monogeneans, trematodes, and nematodes, resulting in tissue lesions of varying severity, depending on the parasite and the host’s immune status. Temporal analysis revealed a significant increase in reports of bacterial diseases after 2000, coinciding with the growth of sturgeon aquaculture in Turkey and Romania. Outbreaks of disease exhibited pronounced geographical clustering in the northwestern Black Sea Region and the Danube River. These areas are characterized by intensive aquaculture activity and ecological vulnerability. These findings highlight the importance of coordinated regional surveillance, wider adoption of molecular diagnostics, and incorporation of health management strategies into conservation planning for Acipenseridae populations in the Black Sea Region. Full article

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection remain leading causes of cirrhosis and hepatocellular carcinoma (HCC) worldwide, and continue to represent a major challenge despite the growing contribution of alcohol-related and metabolic dysfunction-associated steatotic liver disease. Direct-acting antivirals now cure most patients with chronic HCV infection, while nucleos(t)ide analogues durably suppress HBV replication, producing a rapidly expanding population of treated and cured patients. Many nonetheless retain residual fibrosis, portal hypertension and long-term cancer risk, creating a need for non-invasive long-term liver assessment. Multiparametric ultrasound (MPUS) integrates the evaluation of morphology, fibrosis, steatosis, haemodynamics and perfusion within a single examination. This narrative review summarises the evidence supporting MPUS in chronic viral hepatitis, covering elastographic fibrosis assessment, Baveno VII liver and spleen stiffness criteria for clinically significant portal hypertension, contrast-enhanced ultrasound characterisation of focal liver lesions, and emerging techniques such as microvascular and viscosity-sensitive imaging. Particular attention is given to the confounding effect of inflammatory activity on liver stiffness. MPUS is presented here as a proposed evaluation framework for organising complementary measurements within a single examination, and not as an approach of demonstrated clinical superiority: no comparative or outcome-based study has yet shown that acquiring these parameters together improves clinical decisions relative to the individual techniques applied according to current guidelines. Within this framework, the most plausible role of MPUS in the elimination era is longitudinal assessment of the treated liver, a proposition that requires prospective validation against clinical endpoints. Full article