Search Results (412)

Pollen constitutes the primary source of proteins, amino acids, lipids, sterols, vitamins, and minerals for honey bees. However, not all pollen types provide the same resources or have the same biological value. Its chemical composition changes according to botanical origin, geographic location, and environmental conditions. This variability can influence metabolism, the immune system, oxidative balance, and the ability to resist or tolerate infections. This article examines the available evidence on the relationship between pollen chemical quality and the dynamics of Deformed Wing Virus (DWV) infection in Apis mellifera. The analysis is approached from molecular, physiological, ecological, and seasonal perspectives. Current findings suggest that more diverse and higher-quality pollen diets are generally associated with greater colony survival and improved health status, although their effects on viral load are more heterogeneous and context-dependent. In some studies, pollen intake is linked to a reduction in DWV, whereas in others viral loads remain stable or even increase despite improvements in survival, physiological condition, or colony performance. These differences suggest that pollen may act not only by enhancing resistance to the virus but also by increasing tolerance to infection-associated damage. The potential role of pollen bioactive compounds, particularly flavonoids and phenolic acids, is also discussed. Nevertheless, evidence of direct antiviral action of these compounds in bees remains limited, as many proposed mechanisms derive from other organisms. This synthesis provides an integrative perspective on pollen nutrition and its relevance for colony resilience against viral infections. Full article

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by demyelination, neuroinflammation, and progressive neurodegeneration. While there is a small component of genetic susceptibility to MS risk, environmental factors, including infectious exposures, are gaining increased recognition as playing a critical role in MS initiation and progression. Viral infections, especially by Epstein–Barr virus (EBV), have emerged as strong candidates and triggers of MS symptoms, through antibody-mediated molecular mimicry and B-cell dysregulation. In contrast, parasitic infections, including helminths and select protozoa, appear to exert neuroprotective effects by skewing immune responses toward regulation and tolerance. In this review, we examine antibody-driven mechanisms by which viral pathogens promote autoimmunity in MS and contrast these with parasite-induced immunoregulatory pathways that suppress pathogenic inflammation. We further discuss diagnostic and therapeutic implications, highlighting how insights from infectious immunology may inform novel strategies for MS treatment. Full article

Therapeutic vaccines are a key strategy to achieve the goal of “functional cure” of chronic viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human papillomavirus (HPV), and Epstein–Barr virus (EBV). Various platforms (such as viral vectors, nucleic acid vaccines, recombinant proteins, etc.) have successfully induced strong virus-specific T-cell responses in early trials, but their clinical efficacy is still limited by the immunosuppressive environment formed by the host. The core bottlenecks are severe T-cell exhaustion, viral immune escape, and various forms of local immune tolerance. Therefore, the field is moving toward combination therapies, including reduction of viral load, targeting of immune activation, and inhibition of inhibitory signaling pathways. This article summarizes the preclinical and clinical progress of therapeutic vaccines in the past decade, analyzes the major challenges in vaccine development, and discusses the future development directions in this field. Full article

The high-frequency mutation characteristics of SARS-CoV-2 have posed formidable challenges to the development of vaccines and therapeutic agents. Neutralizing antibodies, which serve as effective tools for prevention and control, have undergone continuous updates and iterations in response to viral mutations. This article provides a comprehensive review of researchers’ efforts to achieve both high neutralizing potency and high mutation tolerance in SARS-CoV-2–targeting neutralizing antibodies. Building on the characteristics of conventional antibodies directed against distinct epitopes on the S protein, it further discusses the research on nanobodies, antibody cocktails, multi-specific antibodies, and other antibody formats and engineering approaches, including artificial intelligence–enabled optimization. Each antibody-based strategy targeting SARS-CoV-2 has its own distinctive advantages and potential applications, providing an integrated perspective to support the continued development of antiviral neutralizing antibodies. Full article

Bacteriophages infecting phytopathogenic bacteria represent promising alternatives for plant disease control; however, some groups, such as filamentous bacteriophages, remain comparatively underexplored. In this study, we present a comprehensive characterization of XaF13, a filamentous bacteriophage that infects Xanthomonas vesicatoria, the causal agent of bacterial spot disease in pepper. Morphological analysis revealed a flexible filamentous virion architecture consistent with members of the family Inoviridae. To refine its genomic features, the XaF13 genome was resequenced through a hybrid approach combining newly generated Oxford Nanopore long reads with previously available Illumina data, resulting in a revised genome of 6965 bp. Comparative genomic analysis and intergenomic similarity assessment revealed low nucleotide identity with related inoviruses, supporting the recognition of XaF13 as a putative novel species based on VIRIDIC species-level thresholds. Phylogenetic reconstruction based on the Zot-like protein placed XaF13 within a broader inovirus lineage and showed that it forms a distinct evolutionary branch. In addition, physicochemical assays revealed that XaF13 remains stable across a broad pH range and tolerates brief exposure to elevated temperatures, whereas chloroform treatment and UV-C radiation reduced viral infectivity over time. Overall, these findings highlight the genomic distinctiveness and in vitro physicochemical stability of XaF13, contribute to a better understanding of filamentous bacteriophage diversity and provide a basis for future studies on its ecological role and possible interactions with phytopathogenic bacteria. Full article

Andes virus (ANDV), a highly pathogenic orthohantavirus, enters host cells through low pH–triggered membrane fusion mediated by the Gc glycoprotein, a class II fusion protein containing a single C-terminal transmembrane domain (TMD). While the ectodomain has been extensively characterized, the role of the TMD in late-stage fusion remains unclear. Here, we investigated the minimal functional length and sequence requirements of the ANDV Gc TMD using site-directed mutagenesis. C-terminal deletion mutants and serine-to-alanine substitutions were evaluated for protein expression, virus-like particle production, cell–cell fusion, pseudotyped vector entry, and hemifusion activity. Deletion of the Gc cytoplasmic tail (CT) or a single C-terminal TMD residue was tolerated, whereas deletion of two or more residues impaired particle production and fusion, indicating that at least 21 of the 22 TMD residues are required for efficient membrane fusion and viral entry. Hemifusion assays showed that deletion of two or three residues, or substitution of the strictly conserved S1121, allowed lipid mixing but blocked progression to full fusion, while deletion of four residues also abolished hemifusion. In contrast, mutation of the less conserved S1126 had minimal effect. These results identify a precise TMD length and a conserved polar TMD residue as critical determinants of fusion pore formation in ANDV. Full article

The role of human leukocyte antigen F (HLA-F) at the maternal–fetal interface (MFI) during viral infection and its regulation by interferon signaling remains poorly understood. Here, we investigated HLA-F expression and regulation in first-trimester trophoblast cells following activation of the type I interferon pathway and viral infection. We demonstrate that HLA-F is significantly upregulated at both mRNA and protein levels in response to Poly(I:C) and IFN-β in a dose- and time-dependent manner, suggesting its regulation as an interferon-stimulated gene (ISG). Zika virus (ZIKV) infection similarly induced HLA-F upregulation over time. In contrast, HSV-2 infection downregulated HLA-F mRNA while maintaining steady protein levels, indicative of virus-specific regulatory mechanisms. Moreover, we identified a soluble form of HLA-F secreted following Poly(I:C) stimulation. These findings reveal that HLA-F is dynamically regulated in trophoblasts during viral challenge and type I IFN signaling activation, supporting its broader immunomodulatory role in antiviral defense and immune tolerance at the MFI. Full article

Background Cytomegalovirus (CMV) infection is a major contributor to morbidity and mortality in recipients of hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), and chimeric antigen receptor T-cell (CAR-T) therapy. While antiviral agents remain the cornerstone of treatment, CMV-specific immunoglobulins (CMVIG) have been utilized as adjunct therapy with variable outcomes. This study aims to evaluate the virological response and tolerability of CMVIG in cases of severe or refractory CMV viremia, with or without CMV disease. Methods: We conducted a single-center retrospective case series of adult recipients of SOT, allogeneic HSCT, and/or CAR-T cell therapy who developed CMV viremia or disease and received at least one dose of CMVIG between May 2017 and May 2023 at our center. Virological improvement within 14 days of starting CMVIG and tolerability of CMVIG are the primary outcome of this study. Results: A total of 33 patients were included. Of these, 29 underwent transplantation [SOT: 48.2%, HSCT: 51.7%], and five underwent CAR-T cell therapy (one post-HSCT). High-risk CMV serostatus was present in 12%. CMV viremia was documented in 32 patients (97%), and tissue-invasive disease was present in 11 patients (33.3%). Virological response, was observed in 65.6% of the cohort. The median time to undetectable CMV viral load following CMVIG initiation was 28 days. CMVIG was well-tolerated. All-cause mortality at 90 days remained high (57%). Conclusion: In this case series, CMVIG demonstrated a virological response rate of 65.6% in patients with severe or refractory CMV infection. While CMVIG was well-tolerated with minimal adverse events, the high mortality rate despite virological response suggests that CMVIG may be insufficient for this critically ill population. Our findings should be interpreted as observational data from a small case series, and prospective controlled trials are needed to establish the true benefit of CMVIG in combination with standard antiviral therapy. Full article

Tomato brown rugose fruit virus (ToBRFV) poses a major threat to global tomato (Solanum lycopersicum) production, as it can overcome conventional resistance genes that are effective against tobamoviruses. In this study, a multiplex CRISPR/Cas9 system was developed to target the SlTOM1 susceptibility gene family (SlTOM1a–d), which encodes host factors essential for tobamovirus replication. Six guide RNAs (gRNAs), designed following 12 off-target analyses, were assembled into a multiplex CRISPR/Cas9 construct using a Golden Gate cloning strategy and introduced into tomato genotypes through an Agrobacterium-based tissue culture transformation procedure. Although primary T₀ transformants exhibited chimeric mutation patterns, stable inheritance and segregation of edited alleles were confirmed in the T₁ generation. Sequence analyses identified diverse indel mutations across target loci, with SlTOM1d exhibiting the highest editing efficiency. Multiplex genome editing successfully generated single-, double-, and triple-mutant combinations, with higher-order mutants displaying the strongest tolerance phenotypes. Following mechanical ToBRFV inoculation, edited T₁ plants exhibited markedly reduced symptom severity, low viral accumulation, and improved fruit health compared to wild-type controls. RT-qPCR analysis further confirmed significantly reduced viral RNA levels, supporting a host-factor-mediated tolerance mechanism. Importantly, edited lines maintained normal growth and agronomic performance. Collectively, these findings demonstrate that multiplex CRISPR/Cas9-mediated targeting of SlTOM1 homologs represents a promising and practical strategy for improving ToBRFV tolerance in tomato breeding programs. Full article

The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for inflammaging that can be predictive of successful aging and used to develop potential strategies for successful aging. Despite high metabolic rates and persistent viral exposure, many bat species have much longer lifespans than would be predicted for mammals of their size. The increased longevity of many bat species is achieved through damage tolerance, regulated inflammasome activity, constitutive basal antiviral defenses, enhanced autophagy–mitophagy, and efficient resolution of inflammation, rather than through heightened inflammatory immunity. The CLSV-6 is introduced as a multidimensional immunotype framework integrating six conserved mechanisms that link bat immunity to bat longevity and to human healthy aging: (1) damage tolerance, (2) autophagy–mitophagy, (3) proteostasis (management of degraded proteins), (4) basal immune readiness without activation, (5) inflammasome regulation, and (6) inflammatory resolution capacity. Together, these mechanisms enable a robust antiviral defense when needed without chronic inflammation. Notably, centenarians converge toward this bat-like configuration. Studies suggest that centenarians often preserve more functional NK cells, better macrophage regulation, and improved anti-inflammatory control, with both bats and humans exhibiting reduced activation of the NLRP3 inflammasome, resulting in greater immune resilience. Building on this framework, functional foods—including polyphenols, fermented foods, and herbal extracts—are proposed as practical strategies to shift human immunity toward bat-like, CLSV-6 immunotype by enhancing cellular quality control, regulating inflammasome activity, strengthening basal antiviral readiness, and supporting inflammatory resolution, thereby redirecting longevity strategies from immune stimulation toward damage containment and repair. This review reframes longevity as an emergent property of integrated immune damage management and provides a mechanistic roadmap for nutritional interventions to engineer healthier human aging inspired by bat immunity. Full article

Endophytic fungi are promising sources of novel antiviral compounds, and the crude extract from Alternaria alternata PO4PR2 has previously shown anti-HIV-1 activity. This study evaluated its efficacy against integrase strand-transfer inhibitor (INSTI)-resistant HIV-1 and its mechanism of action. Key resistance mutations (Y143H, G118R, N155H, and R263K) were introduced into the HIV-1 pNL4.3 clone via site-directed mutagenesis and confirmed through Sanger sequencing. Viral infectivity was assessed in TZM-bl cells, while cytotoxicity was measured using an MTT assay. Antiviral activity was determined through a luciferase-based assay, and integration inhibition was evaluated using integrase activity assays and Alu-gag nested PCR. The extract demonstrated potent inhibition of resistant mutants, with low IC₅₀ values (0.02971–0.1652 μg/mL), and showed minimal cytotoxicity (CC₅₀ = 300 μg/mL), maintaining over 80% cell viability. It inhibited integrase activity by 67%, specifically targeting the strand-transfer step, and significantly reduced integrated viral DNA. Molecular docking of 14 compounds identified coumarin derivatives as key bioactive metabolites, exhibiting mutation-tolerant binding within the integrase catalytic pocket. Overall, these findings highlight PO4PR2 as a promising source of compounds for developing new therapies targeting drug-resistant HIV-1 integrase. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as key drivers of hepatocellular carcinoma (HCC). Unlike HCC caused by viral infections or alcohol, MASLD/MASH-related liver cancer develops within a chronic immunometabolic environment characterized by lipotoxicity, sterile inflammation, fibrogenesis, and remodeling of the microenvironment. In this setting, interleukin-10 (IL-10) has attracted growing attention due to its complex, context-dependent roles in immune regulation and tumor immune tolerance. This review explores IL-10 biology and its connection to MASLD/MASH-associated HCC, emphasizing the paradox that IL-10 may diminish harmful inflammation in early stages while promoting immunosuppressive conditions in advanced disease. To supplement existing research, we performed an exploratory reanalysis of publicly available bulk liver RNA-seq data from a mouse model that progresses from MASLD/MASH to HCC. The reanalysis revealed a receptor- and effector-specific rewiring of the IL-10 pathway: while the expression of canonical signaling genes (Stat3, Jak1, Jak2, Tyk2, Socs3) showed minimal changes across stages, receptor subunits (Il10ra, Il10rb) and IL-10-responsive effectors (such as Scd2, related to lipid metabolism, and Ddit4, involved in mTOR and glycolysis regulation) displayed strong stage-dependent induction. This was accompanied by a decrease in hepatocyte signature profiles and an increase in stromal and immune signatures. These results generate new hypotheses and raise key questions—particularly whether a large portion of IL-10 modulation originates from peripheral or non-parenchymal sources, and whether the transcriptional patterns observed reflect protein-level changes—that will require stage-specific, cell-focused human studies incorporating proteomic and cytokine measurements. Full article

Gene-editing technology provides innovative strategies for coping with crop stress, enhancing resistance to biotic stresses (fungal, bacterial, viral infections) and abiotic stresses (salinity, drought, heavy metals, temperature extremes). The CRISPR/Cas9 system is widely used to knock out susceptibility genes, activate resistance genes, or modulate stress-response genes, yielding many stress-resistant crop varieties. However, off-target effects, chimeric effects, and the complexity of multi-gene synergistic editing limit its application. By optimizing and integrating with other cutting-edge technologies, gene editing is expected to yield highly stress-resistant and high-yielding crop varieties, contributing significantly to sustainable agricultural development and ensuring global food security. Rice, a key staple and model plant, has been extensively studied in gene-editing-based research on stress resistance. The practical potential of gene editing for agricultural improvement has been demonstrated by the effective modification of many genes linked to drought, salinity, temperature extremes, and disease resistance using CRISPR/Cas9 and related technologies. This review discusses gene-editing applications in crop stress research, examining the effects of various stresses on crops and the use of gene editing to develop stress-tolerant varieties. It offers substantial guidance for improving crop stress tolerance through gene editing, creating highly resilient cultivars with greater adaptation to complex, variable environments. Full article

Background: Metallic and metal oxide nanoparticles are increasingly explored as antimicrobial biomaterials in endodontics due to their multi-target mechanisms of action, largely mediated by metal ion release (e.g., Ag⁺, Cu⁺). However, bacterial metal resistance systems, particularly efflux-related proteins, may influence their antimicrobial performance. This study aimed to analyze the prevalence and distribution of metal resistance-associated proteins in bacteria involved in endodontic infections using a bioinformatic approach. Methods: An in silico, cross-sectional bioinformatic analysis was conducted using publicly available genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC). Bacterial species associated with acute apical abscess (AAA), symptomatic apical periodontitis (SAP), asymptomatic apical periodontitis (AAP), and post-treatment apical periodontitis (PTAP) were included. The presence of selected metal resistance-related proteins (CutC, CopA, CzcA, CusA, SilA, P-type ATPase, and PA3920) was assessed using a binary presence/absence framework. Prevalence, group comparisons (Fisher’s exact test), and co-occurrence patterns (Phi coefficient) were analyzed. Results: Metal resistance-associated proteins were widely distributed across all infection types, with prevalence ranging from 70.0% to 82.9% and no significant differences between groups (p > 0.05). CutC was the most prevalent protein, followed by CopA and CzcA, whereas SilA and PA3920 were not detected. Correlation analysis revealed consistent co-occurrence patterns among key taxa, including Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella spp. Conclusions: Metal resistance-related proteins are broadly distributed in endodontic microbiota, indicating a conserved genetic capacity for metal tolerance. These findings suggest that microbial resistance determinants may influence, but do not directly determine, the antimicrobial performance of nanoparticle-based biomaterials. This study provides a hypothesis-generating, bioinformatic framework to support the design and optimization of antimicrobial biomaterials, highlighting the need for experimental validation and integration of phenotypic and biofilm-based analyses. Full article