Search Results (2,248)

Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen of cloven-hoofed livestock. Recombination is one of the mechanisms that contribute to genetic diversity of FMDV and facilitate the generation of new viral lineages, or recombinant forms. While the general patterns of recombination in FMDV are well-known, the temporal dynamics of this process remain unexplored. This study systematically analyzed recombination across 1485 publicly available complete genome sequences of FMDV, collected from 1934 to 2024. In addition to the well-known general recombination pattern with hotspots on the borders of the genome region that encodes capsid proteins VP2-VP3-VP1, we identified serotype-specific recombination patterns. A significant temporal signal required to analyze temporal dynamics was found in serotypes A, Asia1, O, and SAT1 in the VP2-VP3-VP1 genome region. To assess the lifetimes of FMDV recombinant forms, we compared these time-scaled phylogenetic trees with phylogenies for other genomic regions exchanged by recombination events. The median lifetimes of FMDV recombinant forms ranged from 2 to 18 years, depending on the serotype and the nonstructural genomic region involved in recombination. These timescales are comparable to human (+)RNA viruses, such as enteroviruses and caliciviruses. In distinct serotypes, recombination could be more frequent on the 5′ or 3′ border of the capsid-encoding genome region, without a uniform pattern. Full article

Background/Objectives: Polysaccharide-protein conjugate vaccines have proven highly effective, yet they remain limited by manufacturing complexity, cost, and variable performance across serotypes, while carrier proteins can add unwanted immunological and production burdens. To address these constraints, we explored a carrier-protein-free conjugate vaccine concept in which a broadly MHC class II-binding helper epitope (PADRE) replaces the conventional protein carrier to provide T-cell help for a pneumococcal capsular polysaccharide antigen. Methods: Using serotype 15C CPS as a model, we generated CPS–PADRE conjugates and compared designs with or without a putative cleavable motif (RR) at the junction, alongside a conventional protein conjugate as a benchmark. Results: In mice, the CPS–protein conjugate induced the strongest CPS-specific IgG response, whereas CPS–PADRE conjugates elicited clear but overall lower antibody levels. Notably, incorporation of the cleavable motif did not improve immunogenicity and instead reduced humoral responses relative to the non-cleavable design. Conclusion: These findings support the feasibility of carrier-protein-free polysaccharide-peptide conjugate vaccines, while highlighting that cleavable junctions are not universally advantageous and must be empirically optimized for polysaccharide-helper epitope architectures. Full article

Mutations in the Mitofusin 2 (MFN2) gene cause Charcot–Marie–Tooth type 2A (CMT2A). Neurotrophin 3 (NT-3) is an autocrine factor that supports Schwann cell survival and differentiation, axon regeneration and myelination, neuromuscular junction (NMJ) integrity, and mitochondrial function. In this study, we assessed the efficacy of NT-3 gene therapy using the AAVrh74 serotype in the Mfn2^+/− mouse model for CMT2A. Although haploinsufficiency is not reported in CMT2A patients, our model shows some features of CMT2A, including axonal atrophy, muscle atrophy, length-dependent axon loss, and abnormal mitochondria, in muscle in the enzyme histochemistry. Eight-month-old Mfn2^+/− mice received a 3 × 10¹¹ vector genome dose of AAVrh74.tMCK.NT-3 intramuscularly, and functional, electrophysiological, and histological outcomes were assessed six months post-treatment. NT-3 gene therapy in Mfn2^+/− mice significantly improved grip strength and rotarod performance, and ameliorated electrophysiological abnormalities and NMJ denervation in lumbrical muscles. Additionally, our therapeutic approach improved muscle histopathology with reductions in mitochondrial abnormalities and oxidative stress. NT-3 further remodeled carbohydrate metabolism in muscle. Our study indicated that AAV.NT-3 gene therapy has a disease-modifying effect in the Mfn2^+/− model of CMT2A, providing further support for the translational potential of this surrogate gene therapy approach to CMT2A patients. Full article

Background/Objectives: Infant pneumococcal conjugate vaccines (PCV) have significantly reduced pneumococcal morbidity and mortality. Newer vaccines, 15-valent (PCV15) and 20-valent (PCV20), offer broader serotype coverage, potentially preventing more disease. This study estimated the number needed to vaccinate (NNV) to prevent one disease outcome for infant PCV20 and PCV15 programs versus 13-valent PCV (PCV13). Countries from Europe, the Asia-Pacific, and the Americas were included. Methods: A multi-cohort, population-based model estimated the cumulative NNVs for infant programs with PCV20 and PCV15 relative to PCV13 in 21 countries. Outcomes included overall pneumococcal case, hospitalization, and death. The ratio of PCV15 NNVs to PCV20 NNVs was calculated. Probabilistic sensitivity analysis (PSA) and scenario assessments tested results’ robustness. Results: Across 21 countries, the median of country-specific NNV estimates to prevent one pneumococcal case was 13 with PCV20 and 80 with PCV15. Median NNVs to prevent a hospitalization or death were 44 and 568 with PCV20 and 203 and 2203 with PCV15, respectively. PCV20 demonstrated lower NNVs than PCV15 across all countries and outcomes. Median NNV ratios for PCV15 versus PCV20 were 5.1 (case), 4.5 (hospitalization), and 4.2 (death). No clear geographic differences were observed. PSA and scenario analyses indicated stable results with minimal deviations. Conclusions: Infant immunization with PCV20 is associated with lower NNVs than PCV15. To achieve the same disease reduction as PCV20, over five times as many children would need to be vaccinated with PCV15. These findings suggest PCV20 may offer greater public health impact compared with PCV15 in infant immunization programs. Full article

Fowl adenoviruses are opportunistic emerging viruses that spread widely in fowls, infecting birds of all ages, including young broiler chicks. This study aims to genotype the current adenovirus strains associated with inclusion body hepatitis hydropericardium syndrome (IBH-HPS) among infected broilers in Upper Egypt and to evaluate their pathogenic features. In 2024, 100 tissue samples were collected across Assiut and Sohag governorates in Upper Egypt for genetic characterization and pathogenicity evaluation. FAdVs were detected in 22% (11/50) of flocks. Typical FAdV lesions of dead embryos were observed after seven days post egg inoculation. Regarding the PCR assay of the hexon gene, only 8 of 30 samples were confirmed positive at 897 bp, yielding a 26.6% positivity rate. The remaining samples were considered negative using established RT-qPCR protocols for other viral pathogens. Partial sequencing of the hexon gene revealed that FAdV isolates (n = 4) clustered within FAdV species-D serotype 2/11, as determined by phylogenetic analysis. The four isolates shared (98–99%) and (94–100%) nucleotide and amino-acid similarities to FAdV-D of Israeli strains (2019–2020) and contemporary Egyptian isolates (2022), respectively, and low genetic divergence (54–81%) in comparison with other documented species. The amino acid sequence alignment and 3D structure indicate that the four immunogenic HVRs are located in the L1 region of the hexon protein, and that the highly conserved ⁹¹GQMTT⁹⁵, a specific region for FAdV-D serotype 2/11, is present. Regarding pathogenicity, the gross and histopathological findings observed clearly demonstrate the systemic pathogenicity of FAdV-2/11 in the infected group, with a final mortality rate of 30% at seven days post-infection (dpi). The FAdV DNA in hepatic tissues and cloacal swabs was confirmed by the PCR method at 3 dpi and 5 dpi. These results emphasize the circulating of FAdV-2/11 species D in Upper Egypt and highlight the significant need for a single inactivated vaccine that effectively targets the relevant FAdV serotypes to achieve broader and more efficient protection. Full article

Objective: This study provides the first systematic synthesis of the burden of Group B Streptococcus (GBS) colonization and invasive disease in Nigeria, with emphasis on prevalence, serotypes, and sequence types (STs). Method: This systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines and was registered on PROSPERO (CRD420251155310). Searches were conducted across multiple databases, including Scopus, ScienceDirect, Web of Science, PubMed, Dimensions, and African Journals Online, as well as in Google Scholar and Google to identify relevant articles. In total, 426 records were retrieved, of which 43 studies met the inclusion criteria. A random-effects model was applied to estimate the pooled prevalence. Result: The pooled prevalence of GBS colonization in Nigeria was 12.0% (95% CI: 9.0–15.0%). Higher colonization rates were observed in Southern Nigeria (13.0%) than in Northern Nigeria (9.0%). The neonatal colonization rate was 16.0%. Colonization rates were 13.0% in pregnant women and 8.0% in non-pregnant individuals. Human immunodeficiency virus status showed no significant association with GBS colonization among pregnant women (OR = 1.47, p = 0.17). Invasive GBS disease was uncommon (3.0%) and occurred only in neonates. Across included studies, serotypes V and II were the most frequently reported, with ST19, ST182, and ST28 being the predominant STs. Conclusions: GBS colonization is common in Nigeria, with marked regional variation and heightened neonatal vulnerability to invasive GBS infections. Notably, nineteen states lacked surveillance data, highlighting substantial gaps in national monitoring. These findings highlight the importance of strengthening prevention strategies, expanding surveillance coverage, and implementing maternal screening and immunization programs to mitigate the burden of GBS. Full article

Background: Dengue infection (DI) is a mosquito-borne arboviral disease primarily transmitted by infected female Aedes mosquitoes. In Bangladesh, DI poses a substantial public health challenge with recurrent outbreaks and rising incidence rates. This systematic review assesses the epidemiological characteristics of dengue infection in Bangladesh, focusing on demographic, clinical, and geographic trends. Objectives: To analyze dengue prevalence, demographic distribution, clinical symptoms, and serotype patterns in Bangladesh, with an emphasis on urban–rural disparities, gender differences, and serotype evolution. Methods: A systematic search was conducted across PubMed, Scopus, Web of Science, and Global Health (Ovid) databases, reviewing studies published from 2000 to 2024. Following PRISMA guidelines, 25 studies meeting eligibility criteria were selected. Data extraction and quality assessment were independently performed by three reviewers, ensuring methodological rigor. Results: Dengue incidence was higher in urban areas, mainly affecting males aged 20–34, with dengue virus serotype 3 (DENV-3) as the dominant serotype. Fever, headache, and joint pain were the most common symptoms, while severe cases often presented with respiratory and hemorrhagic complications. Acute symptoms like dyspnea and dehydration spread rapidly in densely populated areas. In rural areas, dengue showed a more endemic pattern, with persistent symptoms such as gastroenteritis and muscle pain. Conclusion: Dengue is now firmly endemic in Bangladesh, with clear geographic, demographic, and clinical differences. The dominance of DENV-3 and its association with more severe illness highlight the need for targeted and context specific interventions. Control efforts should prioritize vector management, public education, and continuous surveillance in urban areas, while strengthening community surveillance and primary healthcare in rural settings. Further research on rural transmission and the clinical impact of DENV-3 is essential to guide effective and tailored dengue control strategies. Full article

This study constructed a bioinformatics prediction algorithm for human enterovirus uncoating receptors based on amino acid sequences and physicochemical properties. Based on the availability of uncoating receptor information and three-dimensional (3D) structural data, human enterovirus serotypes were classified into training, validation, and prediction datasets. Using amino acid sequences of receptor-binding sites and their physicochemical properties as model features, a prediction model was constructed using the Naive Bayes algorithm and bioinformatic network analysis method. The results showed that both the training and validation datasets achieved a prediction accuracy of 100%. Among the 56 serotypes in the prediction dataset, the vast majority utilized seven known types of uncoating receptors (e.g., SCARB2, CAR, and ICAM-1), while a minority of serotypes may share the same novel, unknown receptor. This study indicates that uncoating receptors can be accurately predicted based on the amino acid sequences and physicochemical properties of human enteroviruses. Furthermore, the three-dimensional structural features at receptor-binding sites can be reflected through corresponding amino acid sequences and their physicochemical properties. This study facilitates a more in-depth investigations of enterovirus pathogenic mechanisms and provides important insights for the development of vaccines and antiviral drugs. Full article

Bluetongue (BT) is a noncontagious, arthropod-borne viral disease of domestic and wild ruminants caused by bluetongue virus (BTV), an arbovirus of the Orbivirus genus within the Sedoreoviridae family. At least 36 serotypes have been identified globally; recurrent circulation of BTV-1, -4, and -8, along with the recent emergence of BTV-3 in northern Europe, underscores a persistent incursion risk for Mediterranean herds. Key drivers include climate-driven expansion of Culicoides vector niches, windborne dispersal, animal movements, and subclinical reservoirs in cattle and goats. As no specific treatment is currently available, control of bluetongue disease still relies largely on vaccination. Live-attenuated vaccines and inactivated vaccines have reduced incidence, but important limitations persist: risk of reversion and the possibility of reassortment for LAVs; requirement for multiple doses and limited cross-protection for inactivated products; and the absence of DIVA capability for both. As an alternative, next-generation platforms are under active evaluation. Subunit formulations, often VP2 combined with VP5 and/or NS1/NS2 virus-like particles (VLPs), and viral-vectored constructs demonstrate favorable safety, strong humoral and cellular responses, inherent or engineered DIVA compatibility, and potential for rapid updating against emergent serotypes. This review synthesizes recent bluetongue activity across the Mediterranean Basin and provides a critical assessment of both existing and emerging vaccine strategies, with a focus on recommending next-generation platforms that emphasize DIVA-compliant, multiserotype, and adaptable vaccination approaches, supported by integrated surveillance and vector control in the region. Full article

Understanding the intrinsic potential of persistent dengue virus (DENV) replication and survival in vector host cells is critically important. In this study, we investigated to what extent DENV can replicate within the vector host Aedes albopictus C6/36 mosquito cells (cell line routinely used for propagation of DENV in research laboratories). We detected DENV serotype 2 (DENV2) loads in cell culture supernatants collected at different days post infection (3, 19, 33, 60, 90, 120 and 175) and found the presence of capsid transcripts and protein levels in these virus supernatants. Tissue culture infectious dose 50 (TCID50) assay revealed a gradual reduction in viral titers and infectivity from days 19 to 175 post DENV2 infection. Furthermore, infection kinetics with these virus supernatants collected at different days post DENV2 infection demonstrated declining viral replication in naïve C6/36 cells and human endothelial recipient cells. These results provided information on viral replication competence and the persistency of DENV2 infection from days 19 to 175 in mosquito cells. Extracellular vesicles (EVs) isolated from DENV2-infected C6/36 cell culture supernatants showed a progressive increase in EV concentration from day 33 to day 175. While DENV2 loads within these EVs declined over time, their ability to mediate infection in naïve C6/36 and endothelial cells remained constant. Notably, the viral membrane (M) protein was detected in EVs at days 3, 19, and 33 but was absent at later timepoints (days 60, 90, 120, and 175). The prM protein was not detected in any of the samples analyzed. In conclusion, DENV2 exhibits the capacity for persistent infection in mosquito cells, thereby potentially serving as a model for investigating the mechanisms that govern years of long-term and sustained viral infections within the vector host. Full article

Avian reovirus (ARV) infections pose a significant and evolving threat to China’s poultry industry, the world’s largest. Diverse farming systems—ranging from modern intensive operations to traditional waterfowl-poultry polyculture—foster a unique ecological niche for ARV, defined by complex serotypic and genotypic diversity, marked regional variations, potential interspecies transmission between chickens and waterfowl, and recurrent co-infections. Collectively, these factors undermine the efficacy of conventional diagnostic approaches. This review systematically outlines the current epidemic landscape of ARV in China, highlighting the molecular characteristics of prevailing strains (particularly those from waterfowl) and their roles in diagnostic evasion. We critically assess the performance and limitations of existing diagnostic techniques (virus isolation, ELISA, PCR/qPCR) within the Chinese epidemiological setting. Furthermore, we discuss innovative technologies—including multiplex qPCR, CRISPR-Cas systems, and next-generation sequencing (NGS)—that offer potential for developing next-generation diagnostics tailored to China’s specific challenges. Finally, we propose future directions, with an emphasis on standardization, data sharing, and interdisciplinary collaboration to bridge the gap between cutting-edge innovation and on-farm application for precise ARV control. Full article

Invasive pneumococcal disease (IPD) results from the dissemination of Streptococcus pneumoniae to normally sterile anatomical sites such as the bloodstream or cerebrospinal fluid. One of the primary roles of pneumococcal conjugate vaccines (PCVs) used in Romania is to reduce the burden of pneumococcal disease. This single-center retrospective study provides an updated overview of IPD epidemiology in a Romanian tertiary hospital. We analyzed 67 IPD cases identified between 2017 and 2023, of which 45 isolates underwent whole-genome sequencing followed by multilocus sequence typing. Results of genome sequence analysis revealed a diverse population of pneumococci, underlining the importance of continuous genomic surveillance. Expanded-valency pneumococcal conjugate vaccines (PCVs), particularly PCV20, showed markedly improved serotype coverage compared to PCV7 and PCV13, while PCV21 showed serotype coverage comparable to that of PCV13. Antimicrobial susceptibility testing revealed sustained resistance to beta-lactams, particularly among meningitis isolates, underscoring the need for targeted antibiotic stewardship and continuous monitoring of local resistance trends. Overall, these findings highlight the evolving epidemiology of invasive pneumococcal disease in Romania, in the post-PCV era, and the need to adapt vaccination and treatment strategies accordingly. Full article

Background/Objectives: Adeno-associated virus serotype 9 (AAV9) can cross the blood–brain barrier, making it widely used as a gene delivery vector for central nervous system (CNS) applications. Despite extensive use of AAV9 in translational research, variability in study designs makes cross-comparisons difficult to interpret. We designed a study in mice to generate a resource of AAV9 biodistribution across tissues for commonly used routes of administration and treatment ages. Methods: Lumbar intrathecal, intracerebroventricular, lumbar intrathecal and intracerebroventricular combination, or intravenous injections of vehicle or AAV9/GFP were performed in C57BL/6J male and female mice on postnatal day 1, 5, 10, or 28. Organs were collected at postnatal day 56 and biodistribution of AAV9/GFP was evaluated by quantifying GFP protein expression and vector genome copy number. Results: Direct cerebrospinal fluid injections led to higher transgene expression levels in the brain and spinal cord compared to intravenous administration but did not de-target transgene expression in peripheral tissues. Lumbar intrathecal and intracerebroventricular combination injections resulted in expression throughout the CNS but did not substantially increase expression in either the spinal cord or brain beyond the levels obtained with the respective single routes. Treatment age had effects on AAV9 biodistribution regardless of the route of administration, especially in the brain, eye, and liver. Conclusions: Our results provide the necessary biodistribution data to establish a standardized benchmark for comparison of the current gold standard AAV9 to next generation viral vectors. Additionally, this body of work can provide valuable insights for the design of translational gene therapy studies. Full article

Dengue is considered the most prevalent mosquito-borne arboviral disease worldwide, representing a public health challenge as its incidence has tripled in the last 30 years. The World Health Organization reports 390 million infections annually in more than 129 countries, with approximately 96 million symptomatic cases and around 40,000 deaths. Mexico is a hyperendemic country, with high prevalence and significant outbreaks. In 2024, a surge was observed, with approximately 125,000 infections and nearly 480 deaths. The states with the most cases and deaths were Colima and Jalisco, respectively, placing significant strain on healthcare services and driving up costs. The disease’s epidemiology from 2014 to 2025 is characterized by marked seasonality and periodicity, and by the simultaneous circulation of all four serotypes. In recent years, a notable increase in DENV-3 has been observed. In 2025, there were 21,981 confirmed cases; Sonora recorded the highest incidence, while Jalisco and Sinaloa reported the highest number of deaths. This study provides a unique decadal analysis of the epidemiological characteristics of dengue in Mexico, highlighting potential challenges and emphasizing the importance of epidemiological surveillance and future approaches, such as vaccine provision in the country, to mitigate the high mortality rate and associated costs. Full article

Epizootic haemorrhagic disease virus serotype 8 (EHDV-8) emerged in southern Europe in 2022–2023, but clinical and pathological characterization in free-ranging wildlife remains limited. This study investigated EHDV-8-associated morbidity and mortality in wild ruminants in a 2023 outbreak in Sierras de Cazorla, Segura y Las Villas Natural Park (Jaén, Andalusia, Spain). Moribund animals demonstrated a consistent acute neuro-respiratory syndrome characterized by weakness, ataxia, nystagmus and severe dyspnoea with frothy oral discharge. On the carcasses of 39 red deer, two fallow deer, and one mouflon, necropsy was performed and subsequently histopathology and a real-time polymerase chain reaction (RT-PCR) on the collected samples. Gross lesions included marked pulmonary oedema, tracheal foam and widespread congestion, while histopathology revealed lymphoid depletion, pulmonary haemorrhage, vascular injury and renal tubular necrosis. All animals tested positive for EHDV-8 with low RT-qPCR cycle threshold values, indicating high viral loads. This series provides the first confirmed clinical, pathological, and molecular evidence of EHDV-8 infection in fallow deer and mouflon in Europe. The observations demonstrate that EHDV-8 causes a peracute systemic haemorrhagic disease in susceptible wild ruminants and underline the importance of integrated wildlife surveillance and timely diagnostic sampling during peak vector activity. Full article