Search Results (1,794)

Viral zoonoses represent a critical intersection of global health, ecology, and ethical issues. Pathogens that pass from animals to humans. This review examines the complex landscape of viral zoonoses, including their mechanisms, impact, and mitigation strategies. We begin with insights into the historical context and significance of these diseases and then explore spillover mechanisms influenced by genetic, ecological, and anthropogenic factors. This review covers the host range, transmission dynamics, and immunological barriers, including viral detection, adaptation, and immune evasion. Genomic insights have revealed the genetic determinants of host switching and adaptation, illuminating the dynamics of viral spillover events. We emphasize the anticipation and prevention of zoonotic events, highlighting surveillance, early warning systems, and the “One Health” approach. Using case studies of outbreaks such as Ebola, avian influenza, and COVID-19, this review examines the real-world consequences of zoonotic diseases. We then discuss interventions, including mitigation strategies and vaccination, and their ethical and social implications. Drawing on past outbreaks, we provide recommendations for the future, aiming to balance human health, conservation, and animal welfare. This review aims to inform professionals, academics, and policymakers by offering a multidisciplinary perspective on the complex world of viral zoonoses and strategies to protect global health. Full article

Duck viral hepatitis (DVH), a highly contagious disease, is caused primarily by duck hepatitis A virus (DHAV). The viral genotypes exhibit significant diversity, creating a challenge as monovalent vaccines fail to provide cross-genotype protection in ducklings. This study aimed to design a multi-epitope peptide vaccine targeting different genotypes of DHAV. Using immunoinformatics approaches, we systematically identified key antigenic determinants, including linear B-cell epitopes, cytotoxic T-cell epitopes (CTL), and helper T-cell epitopes (HTL). Based on these, a novel vaccine candidate was developed. The vaccine construct was subjected to rigorous computational validation: (1) Molecular docking with Toll-like receptors (TLRs) predicted immune interaction potential. (2) Molecular dynamics simulations assessed complex stability. (3) In silico cloning ensured prokaryotic expression feasibility. Then, we conducted preliminary experimental validation for the actual effect of the vaccine candidate, including recombinant protein expression in E. coli, enzyme-linked immunosorbent assay (ELISA) quantification of humoral responses, and Western blot analysis of cross-reactivity. ELISA results demonstrated that the vaccine candidate could induce high-titer antibodies in immunized animals, with potency reaching up to 1:128,000, and the immune serum showed strong reactivity with recombinant VP proteins. Western blot analysis using duck sera confirmed epitope conservancy across genotypes. Collectively, the multi-epitope vaccine candidate developed in this study represents a highly promising broad-spectrum strategy against DHAV. The robust humoral immunity it elicits, coupled with its demonstrated cross-reactivity, constitutes compelling proof-of-concept, laying a solid foundation for advancing to subsequent challenge trials and translational applications. Full article

Background/Objectives: Molnupiravir (MOV) and nirmatrelvir (NMV) are antiviral drugs that were FDA-approved under the emergency use authorization (EUA) for coronavirus disease-2019 (COVID-19) treatment. MOV and NMV target the viral RNA-dependent RNA polymerase and main protease, respectively. Paxlovid is a combination of NMV and ritonavir (RTV), an inhibitor of the human cytochrome P450-3A4 (hCYP3A4). In this study, the structural consequences in the hCYP3A4 caused by MOV-induced mutations (MIM) were evaluated using in silico tools. Methods: MOV-induced mutations (MIM) were inserted into all the possible hotspots in the active site region of the hCYP3A4 gene, and mutant protein models were built. Structural changes in the heme-porphyrin ring of hCYP3A4 were analyzed in the presence and absence of substrates/inhibitors, including RTV. Molecular dynamics (MD) simulations were performed to analyze the effect of MIM-induced structural changes in hCYP3A4 on drug binding. Results: MD simulations confirm that MIMs, R375G and R440G in hCYP3A4 severely affect the heme-porphyrin ring stability by causing a tilt that in turn affects RTV binding, suggesting a possible inefficiency in the function of hCYP3A4. Similar results were seen for amlodipine, atorvastatin, sildenafil and warfarin, which are substrates of hCYP3A4. Conclusions: The current in silico studies indicate that hCYP3A4 containing MIMs can create complications in the treatment of COVID-19 patients, particularly with co-morbidities due to its functional inefficiency. Hence, clinicians must be vigilant when using MOV in combination with other drugs. Further in vitro studies focused on hCYP3A4 containing MIMs are currently in progress to support our current in silico findings. Full article

Bovine parainfluenza virus type 3 (BPIV3) is a significant pathogen implicated in bovine respiratory disease complex (BRDC), leading to lung tissue destruction, immunosuppression, and subsequent bacterial infections in cattle, hence incurring considerable economic losses globally. Notwithstanding its importance, a limited number of commercial vaccinations are presently accessible. The fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, as protective antigens of the Paramyxoviridae family, can elicit neutralizing antibodies and are regarded as optimal candidates for the creation of genetically modified vaccines. A multi-epitope-based peptide vaccine (MEBPV) was developed by immunoinformatics methodologies by choosing epitopes from the F and HN proteins characterized by high antigenicity, moderate toxicity, and limited allergenic potential. The epitopes were combined with suitable linkers and adjuvants to produce the vaccine, whose physicochemical qualities, immunological attributes, solubility, and structural stability were improved and evaluated using computational methods. Molecular docking and molecular dynamics simulations demonstrated the strong potential binding affinity and stability of the vaccination with TLR2, TLR3, and especially TLR4 receptors. Immune simulations forecasted strong humoral and cellular responses, accompanied by a significant elevation in interferon-γ (IFN-γ) production. The vaccine sequence was later cloned into the pET-28a (+) vector for possible expression in Escherichia coli. Despite in silico predictions suggesting a favorable immunogenic potential, additional in vitro and in vivo studies are necessary to confirm its protective efficacy and safety. This research establishes a solid foundation for the creation of safe and efficacious subunit vaccines targeting BPIV3 and presents novel perspectives for the formulation of vaccinations against additional viral infections. Full article

Grapevine leafroll disease (GLD), caused by a complex of grapevine leafroll-associated viruses (GLRaVs), is among the most widespread and economically damaging viral diseases of grapevine. While its physiological and yield impacts are well recognized, the broader ecological implications for vineyard ecosystems remain poorly understood. This review integrates traditional literature analysis with bibliometric approaches to synthesize current knowledge on GLRaV occurrence, diversity, host responses, epidemiology, diagnostics, and management. Data from 729 peer-reviewed articles were categorized into six research clusters: global occurrence and first reports, viral diversity and characterization, host–pathogen interactions, epidemiology and vector dynamics, effects on vine physiology and fruit composition, and diagnostic and management strategies. Our findings highlight GLRaVs as dynamic pathogens shaped by genetic variability, human-mediated plant trade, and ecological interactions with vectors and vineyard biodiversity. Knowledge gaps persist regarding mixed infections, underexplored viticultural regions, ecological impacts, and sustainable management. Future work should prioritize high-resolution genomics, multi-omics approaches, improved diagnostics, ecological studies, and innovative management tools. By framing GLD not only as an agronomic but also as an ecological challenge, this review provides a foundation for more holistic strategies to safeguard vineyard health and productivity. Full article

The phylum Nematoda is host to a vast and diverse virosphere, yet severe viral diseases are rarely observed. This paradox between pervasive infection and limited pathology suggests the existence of a highly effective host–virus “truce”. In this review, we argue that this truce is not a result of viral attenuation but is actively arbitrated by a multi-tiered host immune network, whose primary characteristic is not destructive power but exquisite cost–benefit management. We deconstruct this network into two functional tiers. The first, the “effector layer”, comprises a diverse arsenal of antiviral pathways, including RNA interference (RNAi), the Intracellular Pathogen Response (IPR), and other direct-acting mechanisms. The second, the “regulatory layer”, acts as a command hub, integrating internal physiological states—such as metabolism and aging—with external threat signals to orchestrate a proportional defense, thereby mitigating the high fitness costs of immunity. Understanding this intricate network is critical, as it not only explains the dynamics of infection within nematodes but also has profound implications for a broader medical landscape, particularly through the “Trojan Horse” effect, where nematode-borne viruses might elicit immune responses in their final vertebrate hosts. Together, these insights provide a unified framework for studying nematode–virus interactions and for comparing antiviral strategies across metazoans. Full article

The COVID-19 disease outbreak is the deadliest viral pandemic our generation has experienced, and much uncertainty remains over the varying vulnerability of different populations to the virus. This study investigates whether long-term evolutionary processes, such as genetic diversity and culturally embedded behavioural norms, can help explain why countries experienced different levels of COVID-19 infections and mortalities. Using a sample of 133 countries, we find that populations with higher expected genetic heterozygosity and greater historical exposure to infectious diseases are associated with lower COVID-19 case and death rates. We reveal two distinct pathways through which these effects manifest. Firstly, populations that migrated further from the evolutionary origins of Homo sapiens in East Africa exhibit lower genetic heterozygosity, which, in turn, is linked to greater susceptibility to COVID-19. Secondly, regions with higher historical disease prevalence tend to develop collectivist cultural norms and behaviours that are shaped to reduce disease transmission, which appear to mitigate the spread of COVID-19. These findings suggest that differences in vulnerability are not random but rather deeply rooted in genetic and cultural evolution. The analysis remains robust after accounting for socioeconomic, geographical, and institutional controls. Our findings offer policymakers fresh perspectives by integrating genetic theory and sociocultural dynamics into contemporary public health strategies. Full article

West Nile Virus (WNV), a mosquito-borne flavivirus first identified in Uganda in 1937, has emerged over the past quarter century as a major global public health threat. Since its introduction into North America in 1999, WNV has become the leading cause of arboviral neuroinvasive disease, with recurrent outbreaks continuing across Europe, Africa, and the Americas. This review provides a comprehensive overview of the microbiology, epidemiology, and clinical impact of WNV. We discuss the molecular biology of the virus, highlighting its genomic organization, replication strategies, and the structural and non-structural proteins that underpin viral pathogenesis and immune evasion. The complex enzootic transmission cycle, involving Culex mosquitoes and diverse avian reservoir hosts, is examined alongside ecological and climatic determinants of viral amplification and spillover into humans and equines. The clinical spectrum of WNV infection is outlined, ranging from asymptomatic seroconversion to West Nile fever and life-threatening neuroinvasive disease, with particular emphasis on risk factors for severe outcomes in older and immunocompromised individuals. Current approaches to diagnosis, supportive management, and vector control are critically reviewed, while challenges in vaccine development and the absence of effective antiviral therapy are underscored. Finally, we address future research priorities, including therapeutic innovation, predictive outbreak modeling, and genomic surveillance of viral evolution. WNV exemplifies the dynamics of emerging zoonotic diseases, and its persistence underscores the necessity of a coordinated One Health approach integrating human, animal, and environmental health. Continued scientific advances and public health commitment remain essential to mitigate its enduring global impact. Full article

Artificial intelligence (AI) is increasingly transforming biomedical research and patient care by integrating complex biological, radiological, and healthcare information. In the field of viral respiratory infections, AI-driven approaches have shown great promise in elucidating the complexity of lung immune responses and the dynamic interplay between host and pathogen. Applications include predicting cytokine storm and acute respiratory distress syndrome (ARDS), integrating imaging findings with immunological and laboratory data, and identifying molecular and cellular signatures through single-cell and multi-omics analyses. Similar methodologies have been applied to influenza and respiratory syncytial virus (RSV), providing insights into the mechanisms distinguishing protective from maladaptive pulmonary immunity. This narrative review summarizes current evidence on how AI can evolve into a form of translational intelligence, capable of bridging mechanistic immunology with clinical application. The review explores AI-based models for disease severity prediction, patient stratification, and therapeutic response assessment, as well as emerging approaches in drug repurposing and vaccine response prediction. By integrating biological complexity with clinical context, AI offers new opportunities to uncover immune signatures predictive of antiviral or immunomodulatory efficacy and to guide personalized management strategies. Full article

Myalgic Encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a debilitating and heterogeneous disorder marked by persistent fatigue, post-exertional malaise, cognitive impairment, and multisystem dysfunction. Despite its prevalence and impact, the molecular mechanisms underlying ME remain poorly understood. This review synthesizes current evidence on the role of DNA, both nuclear and mitochondrial, in the susceptibility and pathophysiology of ME. We examined genetic predispositions, including familial clustering and candidate gene associations, and highlighted emerging insights from genome-wide and multi-omics studies. Mitochondrial DNA variants and oxidative stress-related damage are discussed in relation to impaired bioenergetics and symptom severity. Epigenetic modifications, particularly DNA methylation dynamics and transposable element activation, are explored as mediators of gene–environment interactions and immune dysregulation. Finally, we explored the translational potential of DNA-based biomarkers and therapeutic targets, emphasizing the need for integrative molecular approaches to advance diagnosis and treatment. Understanding the DNA-associated mechanisms in ME offers a promising path toward precision medicine in post-viral chronic diseases. Full article

Viruses account for the most abundant biological entities in the biosphere and can be either symbiotic or pathogenic. While pathogenic viruses have developed strategies to evade immunity, the host immune system has evolved overlapping and redundant defenses to sense and fight viral infections. Nutrition and metabolic needs sculpt viral–host interactions and determine the course and outcomes of the infection. In this review, we focus on the hexosamine biosynthesis pathway (HBP), a nutrient-sensing pathway that controls immune responses and host–viral interactions. The HBP converges on O-GlcNAcylation, a dynamic post-translational modification of cellular proteins, that emerged as a critical effector of immune cell development, differentiation, and effector functions. We present a broad overview of uncovered O-GlcNAc substrates identified in the context of viral infections and with a functional impact on antiviral immunity and viral restriction, or conversely on exacerbating viral-induced pathologic inflammation or viral oncogenesis. We discuss the clinical implications of these findings, current limitations, and future perspectives to harness this pathway for therapeutic purposes. Full article

BK polyomavirus (BKPyV) causes severe urinary tract diseases, including BKPyV-associated nephropathy (BKPyVN) and ureteric stenosis, in immunocompromised individuals such as renal transplant recipients. Effective antiviral therapies for BKPyV infection remain an unmet clinical need. While the interferon-stimulated gene 20 (ISG20) exhibits broad-spectrum antiviral activity against RNA viruses, its role and mechanisms against DNA viruses are poorly defined. This study demonstrates, for the first time, potent antiviral activity of ISG20 against BKPyV. This restriction was observed with both endogenous levels of ISG20 and upon overexpression, and this effect was confirmed by ISG20 knockout and immunofluorescence imaging. We observed that ISG20 expression is dynamically regulated during BKPyV infection: it is upregulated both during early infection and by expression of the viral large T antigen (LT) alone. However, endogenous ISG20 expression becomes significantly suppressed during later stages of infection, coinciding with declining LT levels. The physical interaction between LT and both wild-type and mutant ISG20 suggests a potential viral strategy to sequester this restriction factor. These findings establish ISG20 as a novel host restriction factor against BKPyV and suggest that BKPyV employs LT-mediated mechanisms to evade or counteract ISG20’s antiviral effects. Our results elucidate a complex biphasic interplay between BKPyV and host innate immunity, identifying ISG20 as a potential therapeutic target for BKPyV-associated diseases. Full article

A central challenge in functional genomics is understanding the difference between correlative transcriptomic observations and definitive causal understanding of gene function in vivo. Poultry skeletal muscle, a system of significant agricultural and biological importance, demonstrates this challenge. While transcriptomic studies have cataloged extensive RNA expression dynamics during muscle development and in growth-related myopathies like wooden breast, establishing causative roles for these molecules is lacking. This review synthesizes how advanced genetic tools are now enabling a shift from correlation to causation in avian muscle biology. We detail how viral vectors (e.g., adenovirus, lentivirus, and RCAS) and CRISPR/Cas9 systems have provided direct in vivo validation of the functional roles of specific mRNAs, miRNAs, lncRNAs, and circRNAs in regulating myogenesis, hypertrophy, and atrophy. We contrast this success in fundamental biology with the study of myopathies, which remains largely descriptive. Here, a wealth of transcriptomic data has identified dysregulated pathways, including ECM remodeling, metabolism, and inflammation, but functional validation for most candidates is absent. We argue that the critical next step is to apply this established functional genomics toolkit to disease models. By defining causal mechanisms, this research will not only address a major agricultural issue but also provide a model for using genetic tools to dissect complex traits in a post-genomic era. Full article

To investigate the role of epidemic predictors in the mpox outbreak in Africa. This was a retrospective analysis of national-level mpox surveillance data from 20 mpox-affected African countries from January through December 2024. Predictors included viral clades, gross domestic product (GDP) per capita, and population density. A negative binomial regression model estimated the incidence rates ratio (IRR) [95% confidence interval] for mpox incidence and mortality. Random forest models assessed the influence of each predictor in the epidemic dynamic. Clade II was associated with lower mpox incidence (IRR = 0.15 [0.02–0.97]) and mortality (IRR = 0.09 [0.01–1.72]) compared to Clade I. GDP per capita was associated with a 95% reduction in cases count per US $1000 (IRR = 0.05 [0.38–0.74]). Population density was not significantly associated with mpox incidence or mortality. Random forest analysis confirmed GDP per capita as the strongest predictor of mpox burden. The 2024 mpox epidemic highlights how countries with low GDP per capita and Clade I face greater outbreak burdens. Strengthening health systems and addressing poverty as a key social determinant of health through a multisectoral approach are essential to ensure equitable outbreak prevention, control, and long-term resilience. Full article

Influenza virus is one of the most frequent causes of respiratory infection in humans. Recent studies suggest that extracellular vesicles (EVs)—small particles released by cells during influenza virus infection—can influence the immune response and viral pathogenesis. However, during viral replication, infected cells can also release EVs, which may include different subtypes. This study aimed to purify and characterize viral preparations and EVs using sequential ultracentrifugation methods. Influenza A/H1N1, A/H3N2, and B virus strains were produced in human Calu-3 and A549 cell lines. Viral supernatants then underwent a series of differential ultracentrifugation steps at 3000× g, 17,000× g, and 100,000× g. Dynamic light scattering analysis (DLS) validated size heterogeneity for all three types of EVs. Measurement of infectious virus particles for all three pellets showed virus enrichment at 17,000× g and 100,000× g. Dot blot analysis confirmed the enrichment of virus particles in these fractions and the presence of EV protein. This study demonstrates the presence of EVs in virus preparations and highlights the need for improved separation methods to characterize them better and explore their role in viral infection pathogenesis. Full article