Search Results (2,004)

The efficacy of the host antiviral response against Influenza A virus (IAV), a leading cause of global pandemics, hinges upon the rapid recognition of the pathogen and the prompt activation of immune mechanisms. Nevertheless, the epigenetic landscape that orchestrates this antiviral response remains largely elusive. Here, we identify histone demethylase JMJD2D as a critical regulator in defense against IAV infection. A significant upregulation of JMJD2D expression was observed clinically in response to IAV infection, indicating that JMJD2D may play a role in regulating IAV infection. Indeed, JMJD2D-deficient mice exhibit increased susceptibility to IAV, characterized by elevated viral loads, severe lung tissue damage, and reduced survival rates, suggesting that JMJD2D plays an essential role in defense against IAV infection. Consistently, knockdown or pharmacological inhibition of JMJD2D in lung cells suppressed IAV replication and the IAV-triggered innate immune response. Mechanistically, JMJD2D suppressed IAV infection by removing H3K9me3 at the promoter region of retinoic acid inducible gene-I (RIG-I) and cooperating with NF-κB to enhance the expression of RIG-I, a critical sensor for IAV RNA. This study identifies JMJD2D as an epigenetic rheostat that governs RIG-I-mediated antiviral signaling, highlighting its potential as a therapeutic target for mitigating severe IAV infection. Full article

Background/Objectives: Glioblastoma remains the most lethal primary brain tumor in adults, and progress in oncolytic virotherapy is limited by the lack of immunocompetent models permissive to human-tropic viruses. Methods: Here, murine CT-2A and GL261 glioma and B16 melanoma cell lines were engineered to express human Coxsackievirus and Adenovirus Receptor (CXADR) fused to tagBFP, generating “humanized” tumors that preserve parental growth characteristics while acquiring high susceptibility to group B Coxsackieviruses (CVBs) and adenovirus serotype 5. Results: CXADR expression in CT-2A, GL261, and B16 cells markedly enhanced binding, internalization, and replication of CVBs in vitro, with the strongest effect observed for LEV14 (attenuated CVB5), which reached up to 10⁵-fold higher viral titers in humanized cells compared with parental cells. Unchanged sensitivity to vesicular stomatitis virus indicated receptor-specific effects. Humanized CT-2A-CXADR-BFP and GL261-CXADR-BFP cells initiated aggressive subcutaneous and intracranial tumors in syngeneic C57BL/6 mice without signs of immune rejection, and histology and MRI confirmed invasive high-grade glioma phenotypes. In intracranial CT-2A-CXADR-BFP tumors, repeated intratumoral LEV14 administration induced extensive tumor necrosis and prolonged survival despite the rapid development of neutralizing antibodies. Systemic intravenous LEV14 dosing produced strong oncolytic activity against subcutaneous CT-2A-CXADR-BFP tumors, as demonstrated by pronounced tumor growth inhibition, long-lasting regression in a subset of animals with gliomas, and improved overall survival. Conclusions: Collectively, these data establish CXADR-humanized models as versatile, immunocompetent platforms for evaluation of CXADR-dependent oncolytic enteroviruses. Full article

Citrus production is increasingly constrained worldwide by rising soil salinity, particularly in arid and semi-arid regions. In Tunisia, the expansion of saline soils represents a major abiotic stress limiting orchard productivity. The identification of salt-tolerant rootstocks has therefore become a priority, especially as alternatives to sour orange (SO, Citrus aurantium L.), which is highly susceptible to Citrus tristeza virus. In recent years, several outbreaks of the disease have been reported in the Cap Bon citrus-growing region, posing an imminent threat to the sustainability of citrus production in Tunisia. This study evaluated the salt tolerance of commercial cultivars (HER, MAR, WN, NH) grafted onto Citrus volkameriana Ten. & Pasq. (CV, Citrus aurantium × Citrus limon (L.) Burm.f.) and three Poncirus trifoliata hybrids (CC, C35, CTR) under irrigation water salinity ranging from 1.1 to 4.1 mS/cm and soil salinity between 1.8 and 3.8 mS/cm. Data were collected between 2020 and 2021 in five young citrus orchards (KHB, OSN, BKN, BSJ, CHK) located in the main citrus-producing region of Tunisia, with key physiological measurements conducted during the high-evaporation period. Salinity increased across most sites during summer 2021, affecting ion homeostasis, Na⁺/K⁺ selectivity, stomatal traits, photosynthetic performance, and growth. The highest leaf Cl⁻ concentration (0.4 meq g⁻¹ dry weight) was recorded in the sensitive HER/CC combination at the OSN site. Increased salinity at OSN was associated with a 0.86% reduction in canopy growth compared to BSJ. Rootstock tolerance was strongly linked to the ability to restrict Cl⁻ accumulation in leaf tissues. Under higher salinity conditions, CV showed superior performance and represents a suitable alternative to SO. Full article

Yellow fever (YF) remains a re-emerging vector-borne zoonotic disease in tropical regions of the Americas despite the availability of an effective vaccine. In South America, the virus is maintained through a jungle transmission cycle involving Haemagogus and Sabethes mosquitoes and non-human primates (NHPs), which act as amplifying hosts and key epidemiological sentinels. This narrative review examines the current status of YF epizootics in South America, with a focus on the role of NHPs in viral circulation, early detection, and spillover risk to human populations. We synthesize recent evidence on epizootic patterns across endemic countries, the differential susceptibility of neotropical primates, and the ecological and environmental drivers influencing transmission, including deforestation, habitat fragmentation, and human encroachment into forested areas. In addition, we analyze current surveillance strategies, including wildlife monitoring, entomological and genomic surveillance, and their integration within a One Health framework. This review highlights that YF epizootics are expanding geographically and are closely linked to environmental change and human–ecosystem interactions. Strengthening integrated, multidisciplinary surveillance systems is essential to improve early detection, guide vaccination strategies, and prevent human outbreaks. These findings underscore the critical importance of operationalizing the One Health approach to enhance preparedness and response to YF in South America. Full article

The eukaryotic translation initiation factor 4E (eIF4E) family plays a dual role in plants, regulating cap-dependent protein synthesis and mediating susceptibility to viruses in the family Potyviridae. In cowpea (Vigna unguiculata (L.) Walp.), an economically important legume cultivated worldwide, the structural determinants of these isoforms remain largely unexplored. This study characterizes the genomic organization, evolutionary history, and conformational dynamics of eIF4E, eIF(iso)4E, and nCBP in cowpea using a multi-omics approach. Genome mining identified three paralogous genes located on chromosomes 4, 6, and 7, showing high synteny with Phaseolus vulgaris. Phylogenetic analysis confirmed nCBP as the ancestral Class I lineage, distinct from the Class II eIF4E and eIF(iso)4E clades. Theoretical models for the isoforms were generated and subsequently validated by molecular dynamics simulations, revealing that while all isoforms preserve the canonical tertiary architecture and an electropositive cap-binding pocket, eIF(iso)4E exhibits superior structural compactness and hydrogen-bond stability. These biophysical features highlight their role as a stable anchor for viral VPg proteins. By elucidating the atomic-level landscape of these factors, we provide a robust structural framework to guide allele mining and genome-editing strategies aiming to engineer virus-resistant cowpea cultivars without compromising agronomic performance. Full article

Puccinia graminis f. sp. tritici (Pgt) is responsible for stem rust in wheat, a disease with worldwide occurrence. Ethylene response factors (ERFs), a group of transcription factors (TFs) responsive to ethylene, are essential for managing stress signaling under biotic and abiotic challenges. However, our understanding of ERF TFs’ function in wheat (Triticum aestivum L.) resistance against the obligate biotrophic Puccinia graminis f. sp. tritici remains limited. In this work, we report our findings of the TaERF109 gene, which is transcriptionally up-regulated by ethylene or Pgt infection. TaERF109 is localized in the nucleus of rice protoplasts. Results obtained using the yeast one-hybrid (Y1H) assay support the conclusion that TaERF109 interacts with the AGCCGCC sequence (GCC-box). Transient knockdown of TaERF109 via virus-induced gene silencing (VIGS) increased wheat susceptibility to Pgt, accompanied by the down-regulation of three pathogenesis-related (PR) genes, TaPR1, TaPR2, and TaPR10, as confirmed via real-time quantitative PCR. In contrast, the Agrobacterium-mediated overexpression of TaERF109 potentiated resistance of transgenic wheat against Pgt. Overall, these results expand the current understanding of the TaERF109 gene’s function in wheat resistance to Pgt. Full article

Currently, epidemiological models can not only be found in epidemiology but also in other research disciplines. However, an interdisciplinary perspective that highlights the commonalities of epidemiological models across disciplines is missing. The goal of the current study is to foster such a perspective. To this end, a methodology is used that sets the current study apart from traditional review studies. Two benchmark epidemiological models formulated in terms of coupled ordinary differential equations, the susceptible–infected–recovered model and the susceptible–exposed–infected–recovered model, are followed through eight disciplines: epidemiology, virus dynamics within humans, computer viruses, drug addiction, voter dynamics, rumor spreading, sales dynamics, and viral marketing. Structural similarities and structural differences across these disciplines within the context of these two models are worked out. It is shown how the exact same mathematical structure can be applied for quite different interpretations across the selected disciplines. It is also shown that more complex model variants exhibit structural differences across research disciplines. In this way, this study helps researchers compare their own works on a structural level with related works in other disciplines. The particular importance of the current study is that it can boost progress in epidemiological modeling by making researchers aware of an interdisciplinary perspective. Full article

Dengue fever (DF) is an acute mosquito-borne infectious disease caused by dengue virus (DENV), primarily transmitted by Aedes aegypti and Aedes albopictus. Nearly 4 billion people worldwide are at risk of infection, and the 2024 epidemic reached an unprecedented scale. Severe cases can lead to hemorrhage, shock, and even death, prompting the WHO to classify it as a potential pandemic pathogen. Current prevention and control measures face prominent bottlenecks, including limited applicable populations for vaccines, lack of specific antiviral drugs, and increasing insecticide resistance in mosquito vectors. Notably, susceptible animal models serve as core tools for elucidating the pathogenic mechanisms of dengue virus, screening antiviral drugs, and evaluating vaccine protective efficacy, holding irreplaceable significance. This review systematically summarizes the characteristics, application scenarios, and research progress of mainstream and potential susceptible animal models, including non-human primates, mice, pigs, tree shrews, and bats. It covers model systems with different immune statuses, genetically modified types, and species-specific traits. Among these, mouse models are the most widely used due to their high flexibility and controllable cost, while non-human primate models have become key carriers for preclinical vaccine evaluation by virtue of their high homology with human immune responses. However, current models generally suffer from core bottlenecks, such as incomplete simulation of core severe phenotypes, insufficient restoration of immune mechanisms, unclear viral receptor mechanisms, and lack of unified standards for inoculation doses and evaluation indicators. These limitations make it difficult to accurately replicate key severe disease mechanisms, including antibody-dependent enhancement (ADE) and cytokine storms. Future model development should focus on core requirements—including intact immunity, broad-spectrum susceptibility, and accurate simulation of clinical pathological features—prioritize solving the simulation challenges of ADE and cytokine storms, and establish standardized experimental systems and evaluation criteria. By comprehensively summarizing the advantages and limitations of the existing models, this review provides a systematic reference for the optimization and upgrading of dengue virus-susceptible animal models. It also holds important guiding significance for promoting the in-depth development of basic dengue research, innovation in prevention and control technologies, and clinical transformation and application. Full article

Despite the remarkable success of antiretroviral therapy (ART) in suppressing human immunodeficiency virus type 1 (HIV-1) replication, viral persistence remains a major barrier to cure. This persistence is sustained by heterogeneous cellular reservoirs in which viral expression is tightly regulated by host-dependent molecular mechanisms. Beyond the canonical cluster of differentiation 4 (CD4+) T-cell reservoirs, HIV-1 establishes long-lived infection in myeloid cells, glial populations within the central nervous system (CNS), and additional non-canonical cellular niches, each characterized by distinct transcriptional, epigenetic, and immune environments. In this review, we synthesize recent advances in understanding how HIV-1 expression, latency, and reactivation are shaped across diverse susceptible cell types. We highlight cell-type-specific mechanisms governing viral integration, chromatin organization, transcriptional elongation, innate immune sensing, host restriction factors, and cytoskeletal regulation. Particular emphasis is placed on how host signaling pathways and immune microenvironments contribute to reservoir stability and heterogeneity, complicating eradication strategies. We further discuss immunomodulatory approaches that seek to modulate viral expression without exacerbating immune activation. By integrating molecular, cellular, and immunological perspectives, this review provides a framework for understanding HIV-1 persistence as a context-dependent process and underscores the need for cell-type-tailored strategies in HIV cure research. Full article

Vaporized free chlorine, primarily present as hypochlorous acid (HOCl), is increasingly used for indoor microbial control; however, virus-dependent susceptibility and its molecular determinants remain unclear. We evaluated virucidal effects under controlled indoor conditions (0–9 ppb) against echovirus 30 (E30), influenza A/H1N1, and human adenovirus type 3 (HAdV3). Infectious titers were quantified by TCID₅₀ assays. Computational fluid dynamics (CFD) simulations and gas-sensor measurements assessed spatial dispersion, and structural analyses examined oxidation-sensitive amino acid residues. Significant reductions in infectivity were observed for E30 (99.0%, p = 0.00727) and influenza A/H1N1 (99.9%, p = 0.000597), whereas no significant reduction was detected for HAdV3 (p = 0.142). Analyses including all data points without outlier exclusion confirmed the robustness of these findings. CFD indicated uniform dispersion, although spatial heterogeneity within the indoor environment cannot be excluded. These findings suggest that viral susceptibility to vaporized HOCl is associated with residue-level composition and structural context; however, this relationship should be interpreted as correlative rather than causal. Moreover, integration of molecular and structural analyses provides a plausible mechanistic framework, although direct biochemical validation remains necessary. Structural analyses showed lower proportions of oxidation-sensitive residues in adenoviral proteins compared with influenza A hemagglutinin (OR = 0.34–0.40, adjusted p < 0.001) and the E30 VP1 intermediate. Residues were clustered in surface-exposed functional domains in susceptible viruses. Full article

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus. Adaptive mutations such as A226V in the E1 envelope protein of CHIKV significantly enhance the transmission efficiency of the virus in Aedes albostriae, leading to multiple rounds of epidemics around the world including the large-scale outbreak in Guangdong Province in 2025. After a viral infection, a significant proportion of patients will progress from acute arthralgia to chronic arthritis that persists. The pathogenesis of the disease involves the persistence of the virus in joint tissues, the persistent inflammatory response with IL-1β, IL-6 and IL-17 as the core mediated by macrophages, possible autoimmune cross-reactions, and individual genetic susceptibility. At present, there is no specific antiviral drug, but important progress has been made in vaccine development against the virus. Vaccines based on live attenuated virus (VLA1553) and virus-like particle (VLP) platforms have been approved for the market and provide a tool to prevent and control this important public health threat. This review synthesizes current knowledge on CHIKV-induced chronic arthritis pathogenesis and recent vaccine advances, providing a framework for understanding disease mechanisms and guiding future prevention strategies. Full article

Oropouche virus (OROV) is an emerging zoonotic arthropod-borne virus of public health importance. The host range of OROV is largely unknown, but antibody evidence suggests that wildlife and livestock species could be susceptible hosts. To identify potential North American mammalian reservoir hosts, OROV replication curves were generated using eight cell lines derived from livestock, wildlife, and domestic animal species (cow, sheep, bison, white-tailed deer, elk, pig, horse, and dog). The virus replicated in all cell lines by 48 h post infection, except for the horse cells. OROV replication success was greatest in the bison cells followed by pig and dog cells. Moderate replication was achieved in the deer, elk, sheep, and cow cells. These results indicate that numerous animal species may be susceptible hosts for OROV, including important agricultural and wildlife species, but pathogenesis studies are required to confirm this finding. Identifying the reservoir hosts for OROV will allow livestock producers, veterinarians, and public health officials to prepare appropriate vector and disease control measures should the virus initiate an outbreak in the United States. Full article

West Nile virus (WNV) is a mosquito-borne flavivirus of growing importance for both human and equine health in Europe. Horses are highly susceptible to neurological disease and, because they share ecological exposure with humans, they represent valuable sentinels for detecting local viral circulation within a One Health framework. However, diagnosis of WNV infection in equines is complicated by the short and low-level viraemia, which limits the sensitivity of molecular assays, and by serological cross-reactivity with related flaviviruses and the confounding effects of vaccination. In this narrative review, we summarise the current diagnostic tools for WNV in horses, including direct detection methods (RT-qPCR, virus isolation, antigen detection) and indirect serological approaches (IgM and IgG ELISA, virus neutralisation tests), and discuss their practical performance and constraints in clinical and surveillance settings. We further examine equine surveillance systems, passive clinical reporting, active serosurveys and sentinel cohorts, and their integration with vector, avian and environmental monitoring. Key challenges include methodological heterogeneity, limited access to confirmatory testing and variable cross-sector data sharing. Finally, we outline future directions, highlighting the need for harmonised laboratory protocols, innovative field-deployable diagnostics, genomic surveillance and integrated, multi-source monitoring systems to strengthen early warning capacity and improve preparedness for WNV outbreaks in equine populations. Full article

Avian influenza (AI) continues to threaten global poultry production, with accumulating evidence suggesting that certain commercial layer lines may exhibit increased susceptibility under specific experimental conditions compared with broiler chickens. This narrative review synthesizes published experimental infection studies identified through a comprehensive PubMed search, focusing on low pathogenic H9N2 and highly pathogenic H5N1, H5N2, H7N7, and H7N9 viruses. Although bird age and production stage varied across studies, consistent disparities in immune regulation and viral replication dynamics have been reported. We critically evaluate host determinants underlying these differences—including microRNAs, major histocompatibility complex polymorphisms, sialic acid receptor distribution, gut microbiota, and hormonal influences—and integrate findings across viral subtypes and pathogenicity classes to inform breed-tailored vaccination, nutritional, and therapeutic strategies. Full article