Search Results (3,118)

Rising antimicrobial resistance has revived global interest in phage therapy, yet its transition to standard clinical practice remains slow. This challenge is not solely due to a lack of efficacy. Instead, we face a fundamental conceptual barrier caused by an “evaluation mismatch.” Traditional regulations treat phages as static chemical molecules—like taking a “snapshot.” However, biologically, phages are dynamic, evolving populations—more like a living “movie.” In this review, we use Schrödinger’s cat metaphor to explain this reality: phage variability is not a defect, but an essential feature. To bridge this gap, we propose a Controlled Evolutionary Platform. By distinguishing between a fixed “Safety Core” and a fluctuating “Adaptive Periphery,” we can manage viral evolution rather than trying to stop it. Ultimately, to integrate phages into modern medicine, we must redefine “consistency”: shifting our focus from preserving a fixed genetic sequence to ensuring the reliable performance of population dynamics. Full article

Dengue fever, with a high proportion of asymptomatic infections, poses a major global public health challenge that traditional surveillance systems frequently underestimate. Wastewater-based epidemiology (WBE) has emerged as a promising approach to monitoring infectious diseases beyond enteric viruses. Dengue virus is shed in urine, feces, and saliva, providing a biological basis for wastewater detection alongside clinical surveillance. This systematic review and meta-analysis synthesize current evidence on dengue virus (DENV) detection in wastewater and evaluate methodological factors influencing detection success in WBE. A systematic literature search using selected databases and predetermined keywords, followed by eligibility screening, resulted in ten studies being included, covering community surveillance and experimental trials. DENV ribonucleic acids (RNA) were most consistently detected and enriched in wastewater solids, indicating this matrix as the most reliable for surveillance. Among concentration methods, ultrafiltration achieved the highest viral recovery efficiency, while reverse transcription digital polymerase chain reaction (RT-dPCR) demonstrated superior sensitivity and precision compared to those of reverse transcription quantitative polymerase chain reaction (RT-qPCR), particularly at low viral concentrations. Storage at −80 °C was critical for preserving RNA integrity. The meta-analysis yielded a pooled DENV positivity rate of 24% (95% CI: 20–28%) after exclusion of outliers. Overall, solid-phase analysis combined with RT-dPCR represents the most sensitive methodological approach across the included studies. Harmonized protocols are needed to support future translation of dengue WBE into community surveillance as current evidence mainly demonstrates methodological feasibility and provides a technical foundation for future public health integration. Therefore, further longitudinal and multi-site validation is required to establish its broader applicability for dengue surveillance. Full article

The epithelium represents the first line of defense against viral infection, yet the precise mechanisms by which viruses penetrate this complex barrier remain incompletely understood. Single-virus tracking (SVT) has emerged as a powerful fluorescence microscopy approach to directly visualize viral dynamics with nanometer spatial precision and millisecond temporal resolution. In this review, we survey recent progress in SVT methodologies, from image-based approaches to active feedback techniques, and assess their capacity to resolve viral behavior in physiologically relevant epithelial models. We further evaluate advances in virus labeling strategies—including fluorescent proteins, organic dyes, and nanoparticles—that enable prolonged observation while preserving infectivity. By integrating developments in optical instrumentation and molecular labeling, SVT is increasingly capable of capturing critical processes, including extracellular diffusion, receptor engagement, internalization, and trans-epithelial transport. Finally, we discuss current challenges, including limited penetration depth, photobleaching, and the complexity of 3D epithelial tissues, and outline future opportunities to extend SVT towards in situ and tissue-level studies. Together, these advances position SVT as a transformative tool to illuminate virus–epithelium interactions and guide therapeutic strategies. Full article

Background/Objectives: The emergence of SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus-vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). Methods: K18-hACE2 mice and LVG Syrian hamsters were vaccinated with a single intranasal dose of MV-014-212 or MV-014-212-delta. Systemic and mucosal immunity were assessed following vaccination, and protection was evaluated following Delta SARS-CoV-2 challenge. In vaccinated hamsters, morbidity, viral shedding, and lung inflammation and injury were also assessed following natural exposure to infected cagemates. Results: A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8⁺ lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against the Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung, and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Conclusions: Intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens. Full article

Waterhemp (Amaranthus tuberculatus (Moq.) J. D. Sauer) is one of the most competitive and herbicide-resistant weed species in soybean cropping systems across North America. While its competitive and adaptive traits are well-documented, its role as an alternative host for plant pathogens remains underexplored. This review synthesizes current knowledge on fungal, bacterial, viral, and nematode pathogens that infect waterhemp and examines the ecological and management implications of these interactions. We discuss how waterhemp may serve as a reservoir for inoculum, potentially influencing disease dynamics in soybean under changing climate conditions. Furthermore, we assess the potential of host-specific pathogens as biological control agents within the integrated weed management (IWM) approach. Despite promising experimental results, several barriers limit large-scale adoption of bioherbicides, including environmental sensitivity, narrow host specificity, challenges in mass production, and regulatory constraints. Understanding weed–pathogen interactions could inform dual-purpose strategies that reduce both weed pressure and disease risk in soybean systems. Further research is needed to optimize biocontrol scalability, assess climate-driven epidemiological shifts, and develop robust integrated weed and disease management approaches. Full article

Dengue virus (DENV) and SARS-CoV-2 are emerging viral pathogens that share overlapping clinical features, including fever, fatigue, and respiratory symptoms, complicating differential diagnosis in endemic regions. Their co-circulation has increased the risk of co-infections, which may result in unpredictable disease progression, increased morbidity, and mortality. This overlap presents a significant challenge in managing outbreaks, as both viruses pose a major public health threat. Vaccines and direct-acting antivirals may be rendered ineffective by viral mutations, making it difficult to address evolving strains. Host-directed antivirals offer a promising alternative, potentially maintaining efficacy against a multitude of variants. Both DENV and SARS-CoV-2 rely on host proteases for viral maturation and entry, with furin playing a crucial role in viral glycoprotein cleavage. In DENV, furin cleaves the prM protein, facilitating virion maturation, while in SARS-CoV-2, the polybasic furin cleavage site in the spike protein enhances viral entry. This makes furin a compelling pan-viral target, where inhibiting furin could reduce viral fitness without relying on viral mutations. This review highlights the therapeutic rationale for targeting furin and discusses luteolin, a furin inhibitor showing antiviral activity against both viruses. Furin-targeted therapies may offer a durable antiviral strategy effective across DENV serotypes, SARS-CoV-2 variants, and co-infection settings. Full article

In 2023, a highly immunogenic live attenuated vaccine based on the Nigeria 75/1 strain was introduced in Kazakhstan to provide protection against PPR. This study presents the results of a three-year animal trial evaluating the vaccine’s efficacy, safety, and immunogenicity. The novelty of this study lies in the long-term (up to 36 months) evaluation of protective immunity in adult animals, as well as in the comparative analysis of immune responses across different age groups and the assessment of viral suppression following challenge infection. Sheep and goats of different age groups were included, including lambs and kids aged 1.5 and 3 months, as well as adult animals aged 2–3 years. The vaccine was well tolerated following a single immunization, and no clinically significant adverse effects were observed in vaccinated animals, apart from only mild transient local reactions. A strong humoral (IgG) response to PPRV antigens was detected in all groups, with the highest antibody titers observed in young animals. Seroconversion was detected in 100% of vaccinated animals by day 21 post-vaccination. Long-term protective immunity (at least 36 months) was demonstrated in adult animals, whereas in young animals early protection was confirmed at 21 days post-vaccination along with subsequent humoral immune dynamics following a single immunization with a 1.0 mL dose of the vaccine (Nigeria 75/1 strain, titer 10^3.0 TCID₅₀/mL). These findings indicate that the vaccine is well tolerated, highly immunogenic, and provides sustained protection in adult animals while inducing early immune responses in young animals. Full article

[Problem] Converting viral tourism popularity into long-term destination sustainability is a central governance challenge in the digital era. [Aim] This study aims to explicitly measure how emotional value mediates the transition from ephemeral online traffic to durable offline place attachment. [Methodology] Adopting a descriptive mixed-methods approach, data were collected through semi-structured interviews with 16 purposively selected participants (including tourists and locals) recruited via on-site intercepts and online snowball sampling. The inclusion criterion required active engagement with Harbin’s digital tourism discourse. Qualitative transcripts were coded using the NVivo 12 software and subsequently converted into panel data. Grey Panel Relational Clustering was then utilized to geometrically track tourist emotional trajectories. [Results] The analysis identified three structural tourist typologies—the Full-Link Empathy Type, Pragmatic Verification Type, and Traffic-Driven Co-conspirator Type—and revealed three corresponding synergistic paths driving online–offline integration: Virtual–Real Isomorphism, Complementarity, and Symbiosis. [Conclusions] The findings demonstrate that sustainable destination resilience depends fundamentally on the qualitative composition of emotional engagement across different tourist types, rather than sheer visitor volume. [Implications] This study contributes an empirically grounded, emotional value-driven framework to sustainable tourism theory, offering differentiated governance strategies for destinations navigating the volatility of platform-driven attention economies. Full article

Crimean–Congo hemorrhagic fever virus (CCHFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) are tick-borne pathogens that cause severe illness and high mortality. Early diagnosis is critical, particularly in resource-limited settings, to enable timely intervention. Host gene expression profiling offers a promising approach to identify potential biomarkers for early detection, disease staging, and logical treatment decision-making. Using a transient IFN-α/β receptor-suppressed mouse model, we performed targeted transcriptomic analysis on blood samples collected at 2, 3, and 4 days after CCHFV or SFTSV challenge. A significant increase in viral load and changes in gene expression were observed as early as two days post-challenge. CCHFV induced a progressively evolving interferon-driven response, while SFTSV triggered rapid, sustained immune activation. Affected targets included interferon-stimulated genes, chemokines, cytokines, Toll-like receptors, and genes associated with viral evasion and innate immune response. Despite shared expression patterns, unique genes were identified as potential biomarkers to distinguish between CCHFV and SFTSV infections. Differential gene expression revealed distinct immune response dynamics, with suppression of critical immune regulatory genes suggesting transcriptional signatures associated with viral evasion mechanisms contributing to disease severity. These findings provide a comparative analysis of molecular pathways and gene expression changes, offering critical insights for biomarker discovery, effective triage, and evaluation of appropriate medical intervention. Full article

Background: A major challenge in antiviral development is the identification of novel virus–host interactions while ensuring therapeutic efficacy and safety. These challenges have renewed interest in phytochemicals derived from medicinal plants as alternative antiviral agents. Objectives: In this study, we investigated the antioxidant, antiviral, and immunomodulatory properties of a Mediterranean Urtica dioica extract (UdE) against SARS-CoV-2 using chemical, biochemical, and in vitro approaches. Methods: The physicochemical properties of UdE were characterized using microtiter assays and HPLC analysis. Cytocompatibility was evaluated in HEK293T, Vero E6, Caco-2, and Calu-3 cell lines while antioxidant activity was assessed using both chemical and cell-based assays. Antiviral activity was evaluated by assessing inhibition of SARS-CoV-2 receptor binding domain (RBD)–ACE2 interaction using ELISA, inhibition of SARS-CoV-2 main protease (Mpro) activity via FRET assay and inhibition of viral entry using SARS-CoV-2 S1 pseudovirus neutralization assay. Results: UdE (100 µg/mL) inhibited RBD–ACE2 binding by 94% and suppressed Mpro activity by 74%, while reducing moderate but significant inhibition of pseudovirus entry (33.6%) at 300 µg/mL dose level in ACE2 expressing HEK293T cells. Immunomodulatory analysis revealed significant suppression of IL-1β and IL-6 production, accompanied by increased TNF-α and IL-8 levels. Conclusions: Collectively, these findings highlight that UdE exhibits multi-target in vitro antioxidant, antiviral, and immunomodulatory activity against SARS-CoV-2; therefore, UdE represents a promising bioactive extract for the management of SARS-CoV-2 infection. Full article

The COVID-19 pandemic highlighted the critical role of serological assays in understanding antiviral immune responses, monitoring vaccine efficacy, and informing public health strategies. This review provides a comprehensive overview of commonly used SARS-CoV-2 antibody detection methods, focusing on binding and neutralization assays. Antibody binding assays, including enzyme-linked immunosorbent assays (ELISAs), chemiluminescence immunoassays (CLIAs), lateral flow immunoassays (LFAs), and multiplex platforms, enable the rapid and high-throughput detection of immunoglobulin isotypes against various viral antigens. Neutralization assays, including live-virus, pseudovirus (PsV), and surrogate assays, offer functional insights into the ability of antibodies to prevent viral entry, though they often require higher biosafety levels and optimization. Serological assays, primarily antibody binding assays and several surrogate neutralization assays, received Emergency Use Authorization (EUA) during the pandemic, supporting seroprevalence efforts. Antibody binding assays and neutralization assays were also widely used in vaccine immunogenicity studies. Despite many standardization initiatives, assay standardization and data harmonization remain challenging and require further efforts. The choice of assay should be guided by study goals: antibody binding assays are preferred for high-throughput monitoring and epidemiological studies, while neutralization assays are essential for assessing functional immunity and variant-specific neutralization and protection. Full article

Senecavirus A (SVA) has rapidly emerged as a globally distributed swine pathogen, with clinical signs mimicking vesicular diseases such as Foot-and-Mouth Disease, posing challenges for timely detection and control. Here, we analyzed 329 complete SVA genomes spanning multiple continents to provide a comprehensive view of its evolutionary dynamics, recombination patterns, haplotype diversity, and global dissemination. Phylogenetic analyses revealed two major lineages: Lineage 1, consisting mainly of early strains from the United States before 2007, and Lineage 2, which emerged post-2007 and subsequently spread across the Americas and East Asia. Recombination was confined to Lineage 2 and concentrated in nonstructural regions, particularly 2C, highlighting intra-lineage genetic exchange as a driver of recent diversification. Haplotype analysis of the 3AB gene identified 170 distinct haplotypes, revealing a star-like network structure consistent with rapid population expansion from a central ancestral variant, while secondary branches reflect ongoing regional diversification. Despite this high genetic variation, genome-wide dN/dS ratios remained below one, and purifying selection was strongest in the N-terminal domains of structural and nonstructural proteins, indicating functional constraints that maintain viral fitness. Time-scaled phylogenetic reconstruction and Bayesian Skyline analysis revealed rapid lineage diversification and a marked increase in effective population size in the early 2010s. Phylogeographic inference further identified repeated introductions from the Americas into East Asia, likely facilitated by swine trade and other anthropogenic factors. Collectively, SVA evolution is driven by frequent mutation and intra-lineage recombination yet constrained by pervasive purifying selection, generating extensive genetic diversity while maintaining functional integrity, with implications for genomic surveillance and targeted control. Full article

In recent years, nanotechnology has made remarkable progress in the fight against infectious diseases. However, the development of safe and effective antiviral drugs remains a challenge, as viruses rely on host cells for replication. Plant-derived, environmentally friendly nanoparticles have gained significant attention due to their low toxicity, which enables them to target viruses without damaging host cells. In this study, we describe the synthesis of silver nanoparticles (AgNPs) using Arctostaphylos uva-ursi leaf extract and explore their potential antiviral activity. The uva-ursi AgNPs were initially characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). We then optimized two different gellan gum/alginate film formulations (1.6:0.4 and 1.2:0.8) as delivery matrices for the AgNPs and assessed Ag⁺ skin permeation using a Franz diffusion cell system. The antiviral potential of the uva-ursi AgNPs—both alone and incorporated into the films—was tested against herpes simplex virus type 1 (HSV-1). Our findings indicate that uva-ursi AgNPs may directly interact with the viral envelope, disrupting the lipid membrane and/or interfering with viral surface proteins. Overall, green-synthesized uva-ursi AgNPs may represent a natural, cost-effective, and safe alternative strategy for managing herpetic infections. Full article

Background/Objectives: Pediatric HIV case-finding and monitoring remain constrained by delayed early infant diagnosis (EID), loss to follow-up, and limited viral load (VL) testing—challenges particularly consequential in the operationally diverse Asia–Pacific region. We systematically reviewed innovations in point-of-care (POC) and near-patient HIV diagnostics and digital monitoring relevant to children and adolescents. Methods: Following a registered protocol (INPLASY2025110058) and PRISMA 2020 guidance, we searched PubMed, EMBASE, Cochrane Library, and WHO Global Index Medicus for studies on POC/near-patient EID and VL testing, dried blood spot (DBS) workflows, and digital monitoring tools. Risk of bias was assessed using RoB 2, QUADAS-2, and MMAT. Results: Fifty-three primary studies were included (39 sub-Saharan Africa, 12 Asia–Pacific, 1 multi-country/global, 1 Americas/Caribbean). Patient selection and flow/timing were common limitations in diagnostic accuracy studies; sample representativeness and nonresponse bias were frequent concerns in implementation studies. The most consistent benefits of POC EID and near-patient VL testing were shorter turnaround times and improved cascade completion when paired with quality assurance and connectivity. Conclusions: POC diagnostics and digital monitoring can help close pediatric HIV cascade gaps, though evidence derives predominantly from sub-Saharan Africa. Impact depends on implementation design. Asia–Pacific programs should prioritize generating context-specific evidence alongside the adaptation of established lessons. Full article

RNA–protein interactions (RPIs), mediated primarily by RNA-binding proteins (RBPs), are central to post-transcriptional gene regulation and govern RNA splicing, transport, localization, translation, and decay. Dysregulation of RBPs and their associated RNA networks contributes to diverse pathologies, including cancer, neurodegenerative disorders, and viral infections. However, profiling RPIs remains a challenge due to their inherent transience, low binding affinity, and shifting spatial dynamics. This review provides a comprehensive and systematic overview of current methodologies for investigating RPIs. We discuss RNA-centric and protein-centric strategies. In addition, imaging-based approaches are evaluated for their capacity to resolve spatial and temporal dynamics of RBP–RNA interactions in situ. We compare these methodologies in terms of resolution, sensitivity, specificity, and biological applicability, emphasizing the importance of integrative strategies for constructing high-resolution, context-dependent RPI maps in physiological and disease settings. Full article