Search Results (3,065)

Background/Objectives: Emerging viral zoonoses represent a growing threat to global public health, with most newly emerging infectious diseases originating from animal reservoirs. Recent outbreaks of monkeypox, Ebola virus disease, Marburg virus disease, Rift Valley fever, and avian influenza highlight the capacity of zoonotic viruses to cross species barriers, spread internationally, and generate substantial health, social, and economic consequences. This review examines the ecological, epidemiological, and biological determinants of viral zoonotic emergence and transmission, with particular emphasis on vaccination and outbreak prevention strategies. Methods: A structured narrative review was conducted using a predefined literature search strategy across major scientific databases. Peer-reviewed epidemiological, clinical, and public health publications published between January 2000 and February 2026 were screened and selected according to predefined relevance criteria. Results: The emergence of viral zoonoses is driven by complex interactions among animal reservoirs, environmental and climatic changes, human behavior, and viral adaptation. Although transmission pathways and clinical outcomes differ among pathogens, common determinants of spillover and outbreak amplification were identified. Current evidence supports the importance of integrated surveillance, genomic monitoring, vaccination strategies, and community engagement as key components of preparedness and response. Emerging preventive approaches targeting pathogen transmission, including transmission-blocking strategies and vector-associated microbiota interventions, may provide additional opportunities for disease control. Conclusions: Strengthening preparedness for emerging viral zoonoses requires coordinated One Health approaches integrating human, animal, and environmental health. Future priorities include the development of next-generation vaccines, expansion of digital and genomic surveillance systems, improved equitable access to vaccines, and innovative interventions aimed at reducing zoonotic spillover and interrupting pathogen transmission. Full article

Rift Valley fever virus (RVFV) and Crimean–Congo hemorrhagic fever virus (CCHFV) are endemic zoonotic pathogens in Senegal, transmitted by mosquitoes and ticks, respectively. Understanding the seasonal and spatial dynamics of their vectors is essential to improve targeted surveillance. This study investigated the abundance, diversity, and viral infection status of vector populations in a transboundary region (Matam) and a non-transboundary region (Thiès) over two seasons from September 2022 to March 2024. We collected mosquitoes using CO2-baited CDC light traps and sampled ticks directly from domestic small ruminants. A total of 6558 mosquitoes across 23 species and 1904 ticks representing seven species were morphologically identified. Mosquito abundance peaked significantly during the rainy season. Conversely, tick diversity increased during the dry season, with Hyalomma rufipes emerging as the predominant species. Crucially, RVFV was detected exclusively in Aedes vexans mosquito pools from the transboundary Matam region, emphasizing the epidemiological risk associated with cross-border livestock mobility. Viral RNA of CCHFV was detected in multiple tick species across both regions and seasons, confirming a sustained, multi-vector enzootic cycle. These findings demonstrate persistent RVFV and CCHFV circulation in Senegal and highlight the critical need for integrated, season-specific vector surveillance frameworks. Full article

Animal infectious diseases impose severe economic burdens on livestock industries, threaten wildlife populations, and compromise food security. Although vaccination remains the cornerstone of disease prevention, conventional vaccine platforms are often constrained by safety, efficacy, or manufacturing scalability. This narrative review provides a comprehensive analysis of the state of the art in herpesvirus-vectored vaccines for veterinary applications, focusing on five well-characterized alphaherpesviruses: Bovine herpesvirus type 1 (BoHV-1), Pseudorabies virus (PRV), Marek’s disease virus (MDV), Equine herpesvirus type 1 (EHV-1), and Duck enteritis virus (DEV). The intrinsic characteristics of herpesviruses, including large, stable genomes; the capacity for foreign gene insertion; broad host tropism; and the ability to elicit robust humoral and cellular immunity, are examined, and their performance is compared with that of traditional vaccine platforms. Key advances in vectored vaccine development are highlighted, from proof-of-concept studies to the creation of advanced multivalent constructs. These approaches demonstrate protective efficacy against a range of significant animal pathogens, including foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus, avian influenza virus, infectious bursal disease virus, and West Nile virus. The literature was identified through systematic searches of PubMed, Google Scholar, and Web of Science (1990–2026), followed by title/abstract screening and reference chaining. Future directions in vector engineering, mucosal delivery, and synthetic biology approaches are considered. Herpesvirus-vectored vaccines represent a versatile platform for enhancing animal health, supporting sustainable agriculture, and mitigating zoonotic risks. Full article

Background: Selecting the most efficient and specific adeno-associated virus (AAV) capsids for gene delivery to the nervous system via minimally invasive routes is critical to gene therapy advancement. While AAV9, rAAV2-retro, AAV-PHP.eB, and AAV-MacpnS1 have demonstrated significant central nervous system (CNS) transduction ability after systemic delivery, their tropism, efficiency, and safety profiles in a developmentally relevant model have yet to be systematically compared. This study comparatively evaluated four capsids after intravenous administration in neonatal C57BL/6 mice. Methods: Transgene expression was quantitatively assessed across multiple CNS regions, as well as in the heart and liver. Associated biochemical indicators of hepatic stress were also evaluated. Results: The resulting transduction profiles were distinct and capsid-specific. Both AAV9 and AAV-MacpnS1 induced widespread CNS transduction and robust peripheral organ expression. However, AAV-MacpnS1-neuronal tropism in the thalamus was superior, and it was also associated with the most prominent biochemical indicators of hepatic stress. In contrast, rAAV2-retro was remarkably specific to the medulla and spinal motor neurons, demonstrating a valuable safety profile. AAV-PHP.eB achieved broad cellular transduction in the spinal cord, but it was the least specific towards cholinergic motor neurons. Furthermore, transduction in DRG neurons using AAV9 and AAV-MacpnS1 was efficient, but that using rAAV2-retro or AAV-PHP.eB was not. Conclusions: These findings provide an “atlas-like” comparative framework that clearly outlines the strengths and limitations of each vector. They also offer valuable guidance on selecting the most suitable AAV capsid for fundamental neuroscience applications and for developing targeted gene therapies, particularly for neurodevelopmental and motor neuron disorders, where intravenous administration in the early stages of life is a promising strategy. Full article

Rare genetic disorders of the central nervous system (CNS) remain some of the most complex and challenging diseases to treat for several reasons. Targeting the CNS, especially the brain, presents one of the greatest obstacles in gene therapy using adeno-associated virus (AAV) vectors. Although various AAVs have been identified for their ability to transduce different cells in the CNS, their effectiveness and efficiency are significantly limited by the presence of neutralising antibodies (NAbs) and restricted cargo capacity. Despite these challenges, our understanding of AAV structure and technological advances continue to enable researchers to develop innovative strategies that have resulted in groundbreaking, FDA-approved therapeutic products now available for Leber congenital amaurosis (LCA) (Luxturna^®), spinal muscular atrophy (SMA) (Zolgensma^®), and the two recent gene therapy products for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi^® and Upstaza^®, which currently hold FDA and EMA approval, respectively. This review aims to highlight recent advances in the field of AAV gene therapy for neurological disorders, identify research gaps, and suggest areas for future investigation to enable potential breakthroughs particularly in neurodegenerative, neurodevelopmental, and neuromuscular disorders. We foresee that more tissue- and cell-specific AAV vectors designed using AI-powered platforms will emerge to precisely and efficiently target specific brain regions, transforming how CNS disorders are treated. Full article

Wesselsbron disease remains an underrecognized mosquito-borne flaviviral disease despite long-standing evidence of ruminant reproductive loss, neonatal disease, hepatic pathology, zoonotic infection, and mosquito-associated circulation. This narrative review critically synthesizes verified evidence on Wesselsbron virus (WSLV) at the animal–human–vector–environment interface, with the specific aim of clarifying why the virus should be considered a surveillance-sensitive One Health pathogen rather than a rare veterinary curiosity. The review integrates classical veterinary pathology, experimental infection studies, human case reports, serological and molecular evidence, mosquito surveillance, ecological suitability modelling, diagnostic-development studies, and recent evidence from molecular epidemiology, camel investigations, and digital histopathology. The review uses an evidence-weighted synthesis to distinguish experimentally and pathologically supported animal disease, confirmed but poorly quantified human infection, mosquito-associated detection, ecological suitability, diagnostic under-recognition, and unresolved reservoir or transmission questions before integrating these domains into a qualitative One Health risk-assessment framework. The evidence supports WSLV as a cause of ruminant abortion, neonatal disease, and hepatic lesions, confirms zoonotic potential, and indicates repeated detection in ecologically relevant mosquito and multi-host contexts. However, current data remain insufficient for robust estimates of animal burden, human incidence, reservoir competence, natural route frequency, or climate-driven expansion. WSLV should therefore be incorporated into targeted differential diagnosis, laboratory readiness, and One Health surveillance where ruminant abortion events, unexplained neonatal disease, compatible mosquito ecology, undiagnosed febrile illness, diagnostic ambiguity, or ecological suitability indicate plausible risk. Full article

Dengue is the most common vector-borne viral disease worldwide, posing an increasing global health threat. Despite its high burden, no approved antiviral treatments or widely applicable vaccines exist, and patient management remains limited to supportive care, underscoring the urgent need for antiviral development. The NS5 protein is a prime antiviral target, owing to its crucial role in viral replication, high conservation across dengue virus (DENV) serotypes and lack of a human orthologue. We conducted a comprehensive sequence-to-structure analysis to identify conserved druggable regions within NS5, integrating large-scale sequence analysis with structural characterization across all four DENV serotypes. We identified four highly promising Consensus Druggable Pockets within the NS5 dimer—CDP1d, CDP3d, CDP5d and CDP12d—that overlap functionally critical regions, alongside 149 new potential hot spot residues. Domain-specific analysis revealed that MTase offers more densely conserved targets, whereas RdRp provides broader druggable surfaces, revealing complementary features for pharmacological modulation. Several identified pockets spatially overlap known inhibitor binding sites, and preliminary docking analyses support their capacity to accommodate small molecules, reinforcing their therapeutic relevance as candidate targets. Collectively, these findings provide a robust framework for the rational design of pan-serotype anti-DENV NS5 antivirals with an enhanced barrier to resistance. Full article

Adenoviral vectors are widely used for gene therapy and vaccine development. To circumvent pre-existing immunity against commonly used human adenovirus type 5, vectors based on rare human serotype or animal adenoviruses have attracted increasing interest. Previously, we constructed vectors based on fowl adenovirus 4 (FAdV-4) and replaced the knob of FAdV-4 fiber2 with that of FAdV-1 fiber1 to generate FAdV4-CF1K vectors with enhanced transduction efficiency in human cells. In this study, we aimed to modify the packaging system to efficiently produce FAdV-4 vectors carrying transgenes toxic to viral replication. Chicken LMH cells failed to form colonies at low seeding densities. We collected used medium from LMH cell cultures and used it as a supplement to adapt LMH cells, generating the colony-competent subclone LMH-C3532. A lentiviral vector encoding a codon-optimized tetracycline repressor (tetR) was transduced into LMH-C3532 to establish a tetR-integrated cell line, LMH-tetR24. An adenoviral plasmid, pKFAV4-CF1K-CtG, was constructed in which a tetracycline operator (tetO)-bearing CMV promoter controlled GFP expression. The SwaI-flanked GFP in this plasmid was replaced with the HA gene from an H5N1 influenza virus to generate pKFAV4-CF1K-CtHA. Linearized adenoviral plasmids were transfected into LMH-tetR24 cells, and recombinant FAdV4-CF1K-CtG and FAdV4-CF1K-CtHA viruses were successfully rescued, amplified, and purified. When infected with FAdV4-CF1K-CtG at various multiplicities of infection (MOI), the progeny virus yield from LMH-tetR24 cells was 4–10 times higher than that from LMH-C3532 cells. For FAdV4-CF1K-CtHA, the yield difference between the two cell lines was even more pronounced, reaching 3–4 orders of magnitude. Overexpression of HA in LMH-C3532 cells negatively affected FAdV4-CF1K-CtHA replication, resulting in smaller and fewer plaques. In conclusion, by separately integrating tetR into packaging cells and TetO into the adenoviral plasmid, we established a system that can be routinely used to package FAdV-4 vectors. Notably, this system facilitates the propagation of FAdV-4 vectors carrying toxic transgenes. Full article

The genetic and antigenic diversity of H5Nx HPAI Gs/GD lineage continues to be a great challenge facing conventional inactivated vaccines. To overcome this challenge, a recombinant herpes virus of turkey (rHVT) vaccine expressing the viral protein 2 (VP2) of infectious bursal disease (IBD) and H5, rHVT+IBD+H5, was developed using computationally optimized broadly reactive antigen (COBRA) technology. In the current study, the protective efficacy of a commercially available vector trivalent vaccine rHVT+IBD+H5 using COBRA technology was assessed. A total of 120 commercial broilers were divided equally into six groups (G1B–G6B). The chickens in G1B–G3B were challenged with the most recent circulating HPAI-H5N1 clade 2.3.4.4.b Egyptian isolate (GenBank accession No. OQ933425) at 28 days old (DO), while the chickens in G4B and G5B were kept as vaccinated (as G1B and G2B, respectively) and non-challenged, and G6B was the non-vaccinated non-challenged group. In G1B, the chickens were vaccinated with Vaxxitek^® rHVT+IBD+H5 at 1 DO and boostered with a commercially available subunit Baculovirus bivalent inactivated H5+ND (Volvac^® B.E.S.T AI+ND) at 10 DO and had a 100% survival rate. The standalone vaccinated chicken G2B, using rHVT+IBD+H5 at 1 DO, had a highly significant survival rate (90%) vs. 0% (100% mortality) in the non-vaccinated challenged control, G3B. All the vaccinated groups had higher seroconversion at 45 DO especially using H5-coated antigen plates for the enzyme-linked immunosorbent assay (ELISA) test. The viral shedding titers and time were evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) in the collected oropharyngeal and cloacal swabs at 3, 5, 7, and 10 days post-challenge (DPC). In conclusion, vaccination with rHVT+IBD+H5 either as a standalone or when boostered with subunit Baculovirus bivalent inactivated ND+H5 resulted in 90 and 100% protection, respectively, without significant difference in the quantity and duration of viral shedding between both groups against HPAI-H5N1 clade 2.3.4.4.b experimental challenge in broilers. Full article

Background/Objectives: Mosquitoes, including Culex quinquefasciatus and Aedes aegypti, are important vectors of dengue fever, Zika virus, West Nile virus, Japanese encephalitis virus, Eastern equine encephalitis virus, etc. Biological control has always been urgent in mosquito prevention due to resistance developing to synthetic insecticides and environmental toxicity by insecticides. Methods: The leaf essential oil of Mosla. chinensis was isolated, and major components were identified via GC-MS, followed by olfactory behavior assays to evaluate its repellent activity against C. quinquefasciatus. Additionally, the odorant-binding protein 1 and odorant-binding protein 2 (CquiOBP1-2) genes were prokaryotically expressed, and their fluorescence competitive binding activities with the active components of essential oils were examined. Results: The bioassays indicated this essential oil greatly repels C. quinquefasciatus, which will significantly protect people against vector-borne diseases. In the fluorescence competitive binding experiments, the CquiOBP1-2 proteins exhibit great binding capacities to volatile components, including Citronellal, Citronellol, Geraniol, Limonene and Isopulegol. Furthermore, the behavioral experimental results also indicate that the mixture of these five ligand compounds has an obvious repellent effect on mosquitoes, highlighting that they may be applied as potential mosquito repellent agents. Moreover, molecular docking and site-directed mutation analysis further confirm Phe123 and Gln77 are both key amino acid residues of CquiOBP1-2 proteins involved in the olfactory recognition of repellent ligand compounds from M. chinensis essential oil. Conclusions: The behavioral experimental verification and the exploration of olfactory molecular mechanisms are helpful to promote the biological control of plant essential oils in mosquito pests. Full article

Background: Viral vectors are indispensable tools in gene therapy and neural circuit mapping, offering promising therapeutic strategies for diverse genetic diseases and advancing neuroscience research. To achieve high transduction efficiency while mitigating impurity-induced immunogenicity, the development of viral vectors with improved purity and quality is essential. However, this critical requirement is often unmet by conventional purification methods such as ultracentrifugation, which are time-consuming and frequently result in limited product purity. The pseudorabies virus (PRV) is extensively employed as a viral tool for mapping neural circuits, where improved purity contributes to enhanced accuracy of neural tracing. PRV531 is a retrograde trans-synaptic tracer modified from the PRV Bartha strain, specifically designed to facilitate the precise visualization of hierarchical neural networks. Methods: In this study, we developed a method for the concentration and purification of PRV531 by integrating hollow fiber ultrafiltration (HF) with Capto^TM Core 700 (CC700) chromatography. Initially, to concentrate the viral supernatant, a 500 kDa HF membrane was employed, maintaining a feed flow rate of 80 mL/min, a shear rate ranging from 2000 to 6000 s⁻¹, and a transmembrane pressure (TMP) between 0.5 and 1 bar. Following concentration, the virus underwent purification through CC700 chromatography, operating at linear flow rates ranging from 100 to 300 cm/h. Results: Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) revealed distinct bands consistent with the expected sizes of major PRV structural proteins, each with molecular weights ranging from 25 kDa to 150 kDa, concurrently demonstrating a substantial reduction in host cell proteins (HCPs) contamination. The purified PRV531 achieved a high final infectious titer of 3.55 × 10⁹ PFU/mL, with an overall functional virus recovery of 8.88% from the crude supernatant to the final product. Conclusion: These data demonstrate that TFF combined with CC700 resin can efficiently purify retrograde trans-synaptic PRV tracer. Furthermore, this approach provides a promising strategy for purifying other viral-based tracers that traditionally rely on conventional centrifugation methods. Full article

Stable cell lines have recently achieved recombinant adeno-associated virus (rAAV) titers comparable to the standard triple transfection approach, making them a promising alternative to plasmid-based production systems. However, whether integration of the rAAV transgene into the host genome influences packaging efficiency and vector quality remains unclear. In this study, we generated stable HEK293 cell lines carrying the rAAV transgene in their genome. rAAV production was enabled by supplying the rep/cap and helper genes on two plasmids, rendering vector genome generation dependent on the chromosomally integrated transgene. Although the stable cell lines produced a 4.5-fold lower titer of viral genomes (VGs) compared to the standard triple transfection method, VG-normalized potency was four times higher. Detailed particle characterization further revealed 3-fold lower plasmid backbone DNA packaging in rAAVs produced by stable cell lines relative to triple transfection. Consistent results were obtained from mass photometry and ELISA/ddPCR analyses for the double transfection condition, while discrepancies emerged under triple transfection. These findings emphasize the importance of functional and qualitative assessments for evaluating different rAAV production approaches. Full article

Dengue Virus (DENV) circulates as four antigenically distinct serotypes whose dominance fluctuates over time in many endemic regions, a phenomenon known as serotype shift that is frequently associated with large outbreaks and increased disease severity. This review, through a synthesis of epidemiological, virological, immunological, entomological, and environmental evidence, observes that serotype shift likely arises from the interaction of multiple determinants rather than solely from viral evolution, with population immunity playing a central role. The accumulation of serotype-specific herd immunity, together with short-lived cross-protection and Antibody-Dependent Enhancement (ADE), reshapes population susceptibility and creates ecological space for heterologous serotypes with higher transmission potential. The synthesis of global dengue studies indicates that these immune dynamics interact with viral genetic diversity, vector competence, climate variability, and human factors such as demography, socioeconomic status, population density and mobility to drive cyclical and sometimes abrupt changes in serotype dominance. Notably, the review indicates that serotype changes often precede or coincide with more clinical severity and patterns of outbreaks, with direct implications for the process of forecasting outbreaks, vaccine performance, and preparedness to respond with appropriate health measures. On the whole, this review confirms the opinion that the change of dengue serotype occurrence becomes a consequence of interconnected biological and ecological processes involved in the transmission of dengue serotype shifts in hyperendemic areas. Full article

O’nyong-nyong virus (ONNV) is a mosquito-borne alphavirus responsible for large-scale epidemics in sub-Saharan Africa. As the closest evolutionary relative of Chikungunya virus (CHIKV), ONNV shares substantial genetic similarity and overlapping clinical manifestations with CHIKV. Mechanistic understanding of ONNV infection has therefore largely been extrapolated from CHIKV rather than directly established. However, ONNV exhibits distinct biological features, including predominant transmission by Anopheles mosquitoes and a clinical presentation characterized by prominent lymphadenopathy with limited acute joint edema. These distinctions underscore the need for an integrated synthesis of experimentally validated determinants of ONNV infection. In this review, we summarize current evidence on molecular and immunological factors regulating ONNV infection in mammalian hosts and mosquito vectors. We first discuss species-specific viral clearance, host dependency factors, intrinsic antiviral restriction mechanisms, protective innate immunity, inflammatory pathology, and mechanism-informed therapeutic strategies in mammalian hosts. We then examine stage-specific immune regulation in Anopheles mosquitoes, emphasizing mechanisms that constrain viral replication while permitting persistent infection and transmission. Finally, we discuss nsP3-dependent vector specificity and the potential contribution of alternative mosquito species to ONNV ecology. Together, this review provides an integrated framework for understanding how host factors, immune responses, and vector-specific adaptations shape ONNV infection, pathogenesis, and transmission. Full article

Insect-mediated transmission is central to the epidemiology of plant viruses and has major implications for global food security and agricultural production. Although several resources have compiled information on plant virus transmission, evidence-traceable integration of virus–insect vector–host plant relationships remains limited. Here, we developed the Virus–Insect–Plant Database (VIP-DB), an evidence-guided database that links literature-derived virus–insect transmission records, host plant information, transmission mode annotations, taxonomic information, and traceable literature evidence. VIP-DB compiles 583 virus–insect transmission relationships, 855 virus–plant relationships with non-missing host plant information, and 1375 integrated virus–insect–plant records. Among these records, 120 lack host plant information and 51 lack transmission mode annotation. VIP-DB provides a curated and searchable resource for querying documented plant virus, insect vector, host plant, and transmission mode information. This database offers an evidence-traceable framework for comparative analyses of plant virus transmission relationships and supports future studies in plant virology, vector ecology, and disease management. Full article