Search Results (355)

O’nyong-nyong virus (ONNV) is a mosquito-borne alphavirus responsible for large-scale epidemics in sub-Saharan Africa. As the closest evolutionary relative of Chikungunya virus (CHIKV), ONNV shares substantial genetic similarity and overlapping clinical manifestations with CHIKV. Mechanistic understanding of ONNV infection has therefore largely been extrapolated from CHIKV rather than directly established. However, ONNV exhibits distinct biological features, including predominant transmission by Anopheles mosquitoes and a clinical presentation characterized by prominent lymphadenopathy with limited acute joint edema. These distinctions underscore the need for an integrated synthesis of experimentally validated determinants of ONNV infection. In this review, we summarize current evidence on molecular and immunological factors regulating ONNV infection in mammalian hosts and mosquito vectors. We first discuss species-specific viral clearance, host dependency factors, intrinsic antiviral restriction mechanisms, protective innate immunity, inflammatory pathology, and mechanism-informed therapeutic strategies in mammalian hosts. We then examine stage-specific immune regulation in Anopheles mosquitoes, emphasizing mechanisms that constrain viral replication while permitting persistent infection and transmission. Finally, we discuss nsP3-dependent vector specificity and the potential contribution of alternative mosquito species to ONNV ecology. Together, this review provides an integrated framework for understanding how host factors, immune responses, and vector-specific adaptations shape ONNV infection, pathogenesis, and transmission. Full article

Carbapenem-resistant Acinetobacter baumannii (CRAB) is considered a persistent clinical problem characterized by high mortality and restricted therapeutic options. The current antimicrobial regimen focuses on active bacteria without taking into account physiological states that influence the treatment response. Biofilm formation, metabolic changes, efflux activity, and membrane remodeling reduce antibiotic activity at infection sites and help bacteria survive despite in vitro susceptibility. Clinical performance is also compromised by inadequate tissue penetration, toxicity, and inconsistent pharmacokinetics, which reduce the ability to maintain effective antimicrobial activity at the target site. Therefore, a new strategy is needed that considers how bacteria behave during infection. Nanotherapeutic systems can optimize antimicrobial delivery by changing drug distribution and enabling sustained antimicrobial release within infected tissues. These properties can improve antimicrobial distribution within biofilms and structurally restricted infection sites. This review proposes a phenotype-guided approach linking dominant bacterial phenotypes with targeted nanotherapeutic intervention. Advances in nanoscale diagnostics and computational analysis allow earlier identification and more precise characterization of resistance features, so treatment decisions reflect the current state of infection. When integrated with nanotechnology, this information supports treatment approaches that adapt to changes in bacterial behavior over time. Extending this concept to host-directed and microbiome-informed interventions provides additional control by addressing factors that sustain infection beyond the pathogen. These elements create an integrated system that connects detection, analysis, and treatment, allowing therapy to match the biological conditions of infection for more precise CRAB management. Full article

Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal alignment, through irregular diet, sleep disturbance, shift work, or social jet lag, may profoundly alter microbial composition and the production of neuroactive metabolites. These alterations have emerged as potential contributors to the pathophysiology of mood disorders. This review introduces the concept of chrono-metabolic psychiatry, a framework integrating circadian rhythms, gut microbiota dynamics, and host metabolic signaling in the development and course of depressive and bipolar disorders. In this framework, the term “chrono-metabolic” refers to the integration of biological timing, host metabolic regulation, and microbiota-derived metabolic signaling. Chrono-metabolic psychiatry therefore shifts the focus from static dysbiosis or neurotransmitter imbalance alone to the time-dependent interactions among circadian misalignment, microbial rhythmicity, immune regulation, metabolite production, and affective instability. Diurnal fluctuations in short-chain fatty acids, tryptophan–kynurenine metabolites, bile acids, and microbial-derived neurotransmitters interact with clock gene regulation, hypothalamic–pituitary–adrenal axis activity, neuroinflammation, and synaptic plasticity. Chrono-disruption may represent a transdiagnostic vulnerability factor and may confirm the bidirectional relationship between mood instability and microbiota rhythmicity. Emerging therapeutic implications, including chrono-nutrition, time-restricted feeding, targeted probiotic administration (“chronobiotics”), and the microbiota-modulating effects of psychotropic medications are discussed. By shifting from a compositional to a temporal–metabolic perspective, this model highlights the importance of microbial oscillations rather than static dysbiosis alone. Integrating circadian biology into microbiota research may enable metabolomic stratification and pave the way for precision psychiatry approaches grounded in host–microbe metabolic crosstalk. Future longitudinal and time-resolved multi-omics studies are needed to validate this framework and to translate it into clinically actionable interventions. Full article

Human metapneumovirus (HMPV) is a major cause of respiratory infections, but its impact on macrophage antibacterial functions remains poorly understood. Macrophages play a crucial role in host defense through phagocytosis, and impairment of this function may increase susceptibility to secondary infections. Here, we show that HMPV infection of THP-1-derived macrophages significantly reduces bacterial uptake in a replication-dependent manner. This effect was restricted to infected cells and was not recapitulated by cell-free supernatants, indicating a cell-intrinsic mechanism. HMPV infection was also associated with reduced expression of the scavenger receptor CD36. Viral gene knockdown studies further implicated the HMPV G protein in this phenotype, as silencing the G protein restored phagocytic function. Analysis of single-cell RNA-sequencing datasets from HMPV-infected mouse lungs revealed reduced CD36 expression and broader alterations in phagocytosis-associated gene programs across lung macrophage subsets. Supporting these observations, expression of Cd36 and Marco was reduced in lung tissue from HMPV-infected mice. Overall, these findings demonstrate that HMPV impairs macrophage-mediated bacterial uptake through a replication-dependent, cell-intrinsic mechanism and identify reduced scavenger receptor expression and the viral G protein as factors associated with this phenotype. These alterations may contribute to increase susceptibility to secondary bacterial infections during HMPV infection. Full article

Soybean mosaic virus (SMV) establishes successful infection through the coordinated action of multiple viral proteins, yet how these components are collectively engaged in host processes remains unclear. Using 10 SMV-encoded proteins as baits, we screened a soybean (Glycine max) cDNA library using the yeast two-hybrid (Y2H) method and obtained 200 positive clones corresponding to 147 nonredundant candidate host proteins. Integrative analyses indicated that these interacting proteins were mainly associated with host processes related to photosynthesis and energy metabolism, as well as protein quality control (PQC), and that their promoters were enriched in light- and stress-responsive elements. Photosynthesis-related genes were more strongly perturbed in the susceptible cultivar, whereas PQC-module genes showed overall downregulation in both resistant and susceptible cultivars upon SMV infection. Y2H, Bimolecular Fluorescence Complementation (BiFC), and transient expression assays identified four soybean resistance factors that interact with SMV proteins. These factors delayed systemic spread and continued to restrict viral proliferation after systemic infection was established. Notably, SMV accumulation partially rebounded when viral proteins were co-expressed with GmSTOP1, GmHrBP1, or GmGIP2, while co-expression of GmSiPPase and NIa-Pro further inhibited viral proliferation. In summary, this study maps the host-targeting profile of SMV across multiple viral components and provides clues to the SMV–soybean interaction network and antiviral gene resources in soybean. Full article

Arthropod-borne viruses (arboviruses) cause a wide range of acute and chronic diseases and represent a growing global health burden. Although some vaccines exist, antiviral therapies remain limited. Identifying host restriction factors may enable new therapeutic strategies. We previously showed that bacterial effector proteins can serve as tools to uncover innate immune defenses. Here, we used a bacterial effector screen in bat cells to identify host factors restricting the arboviruses Sindbis virus (SINV) and O’nyong’nyong virus (ONNV). Several effectors enhanced infection by both viruses. However, we found the Shigella flexneri-encoded E3 ubiquitin ligase IpaH2 to selectively promote SINV replication. IpaH2 enhanced SINV infection across multiple mammalian cell lines, suggesting that it targets a conserved antiviral mechanism, and this effect required IpaH2 E3 ubiquitin ligase activity. Screening of putative IpaH2 host targets identified via ubiquitin-activated interaction trap (UBAIT) assays revealed the host factors ATP-binding cassette sub-family F member 3 (ABCF3) and Plakophilin-2 (PKP2) to play roles in restricting SINV infection. While ABCF3 broadly restricted multiple viruses, PKP2 specifically limited SINV replication, indicating a virus-specific restriction factor. These findings demonstrate that bacterial effector screening can identify both broadly acting and virus-specific host defenses, providing insight into antiviral mechanisms and potential therapeutic targets. Full article

Although hantaviruses have traditionally been considered geographically restricted rodent-borne pathogens, globalization, climate change, ecosystem disruption, and environmental contamination may collectively favor novel transmission scenarios and altered epidemiological patterns. The experience gained during the SARS-CoV-2 pandemic showed the importance of environmental determinants, airborne exposure, and host susceptibility factors in emerging viral diseases. In this context, increasing but still indirect evidence suggests that environmental toxicants and the exposome may modulate susceptibility to hantavirus infection and influence disease severity. The proposed mechanisms include oxidative stress, endothelial dysfunction, pulmonary inflammation, and immune dysregulation, rather than direct causal effects of toxicants on infection itself. This article discusses current knowledge regarding interactions among toxic environmental exposures, climate change, and hantavirus disease, with special emphasis on Andes orthohantavirus (ANDV), the principal hantavirus known to exhibit person-to-person transmission. The article integrates recent evidence within the One Health framework and highlights future research priorities linking environmental toxicology, zoonotic disease ecology, and global environmental change. Full article

BK and JC Polyomaviruses (BKPyV and JCPyV) are ubiquitous human pathogens capable of establishing lifelong, asymptomatic persistence in the majority of the global population. While decades of research have focused on their lytic replication cycles and the development of severe diseases, such as polyomavirus-associated nephropathy (PVAN) caused by BKPyV and progressive multifocal leukoencephalopathy (PML) caused by JCPyV, their primary evolutionary strategy is one of persistence rather than pathogenesis. This review shifts the perspective from a replication-centric framework towards an evolutionary persistence model, detailing the multi-layered host and viral determinants that maintain the homeostatic balance. At the cellular level, viral genomes are restricted by chromatinization into minichromosomes and host S-phase licensing. These constraints are reinforced by innate immune sensing and adaptive T-cell and antibody responses that curtail systemic dissemination while permitting periodic, low-level urinary shedding, which is essential for horizontal transmission. In addition to these host barriers, the viruses utilize intrinsic regulatory mechanisms to prevent excessive replication and immune detection, including the stable archetype non-coding control region (NCCR), viral microRNAs that downregulate early gene expression, and the small t antigen (STAg). Finally, we address unresolved questions regarding the full spectrum of cellular reservoirs, the molecular triggers of reactivation, and the ecological factors shaping their transmission routes. Understanding these maintenance mechanisms is crucial for refining clinical interventions and managing the rare, devastating transitions from silent persistence to lytic disease. Full article

Background: Tooth extraction (TE) after chemoradiotherapy is common in locally advanced nasopharyngeal carcinoma (LA-NPC), yet its determinants remain unclear. We evaluated the association between the Comprehensive Repair–Inflammation Index (CRII), reflecting systemic inflammation and host repair capacity, and TE risk after concurrent chemoradiotherapy (CCRT). Methods: We conducted a retrospective analysis of 354 patients with LA-NPC treated with definitive CCRT. The primary endpoint was post-treatment TE (none vs. ≥1). CRII was calculated from pre-treatment laboratory parameters and analyzed continuously, with a breakpoint identified via segmented regression. Logistic regression and restricted cubic splines were used. Multivariable models adjusted for clinical variables and mandibular dosimetric parameters (mean dose, V50, V60). Results: TE occurred in 70.1% of patients. CRII was significantly higher in those with TE (147.5 vs. 122.0; p < 0.001). CRII was strongly associated with TE (per 10-unit increase: OR 1.49, 95% CI 1.34–1.66; p < 0.001). A nonlinear relationship was observed, with a breakpoint at 145.7, above which TE rates increased markedly (90.5% vs. 58.8%; p < 0.001). CRII remained independently predictive after adjustment (adjusted OR 1.46; ≥145.7: OR 5.1; both p < 0.001). Mandibular dose parameters were not significantly associated with tooth extraction in this analysis. Conclusions: CRII independently predicts post-CCRT TE with a nonlinear risk pattern, highlighting the potential contribution of systemic host-related factors alongside conventional dosimetric parameters. Full article

Background and Aims: Understanding regulatory interactions between hepatitis B virus (HBV) and host factors is essential for the development of next generation host-directed antiviral therapies and the achievement of a functional HBV cure. Here, we investigated HBV-induced alterations in host gene expression in primary human hepatocytes (PHH) to identify host factors exploited by the virus for replication and persistence. Whole-transcriptome sequencing (WTS) of HBV-infected PHH identified host pathways with potential roles in the HBV life cycle. RNA interference-based functional screening of dysregulated candidate genes identified cyclin L1 (CCNL1) as a key host factor. RNAi-mediated knockdown of CCNL1 reduced HBV gene expression, including hepatitis B surface antigen (HBsAg). Mechanistically, CCNL1 regulates phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) at serine 2 (S2), consistent with a role in transcriptional regulation. CCNL1 knockdown further reduced the binding of total and phospho- (Ser2/Ser5) RNAPII, pan-acetylated histone H3 (H3ac), and H3K27ac to HBV covalently closed circular DNA (cccDNA), indicating impaired cccDNA-dependent transcription. In addition, CCNL1 expression was elevated in chronic hepatitis B patients compared with those with resolved infection. Collectively, these data demonstrate that CCNL1 promotes HBV transcription and replication through modulation of RNAPII phosphorylation and chromatin-associated transcriptional activity, identifying CCNL1 as a potential host susceptibility factor for HBV. Importance: Hepatitis B virus infection remains a major threat to human health in areas with high prevalence. There is need to fully understand the complex interactions between the virus and human host factors/processes to support ongoing efforts to develop anti-HBV therapies that can be used with existing therapies to achieve a better cure. HBV relies on host cellular factors and biological processes to establish and maintain efficient infection, making host–virus interactions attractive targets for therapeutic intervention. Thus, identifying host factors that support and/or restrict HBV infection is essential for understanding the molecular basis of chronic HBV infection and for developing host-targeting anti-HBV drugs. This study identifies cyclin L1 (CCNL1) as a host susceptibility factor that promotes HBV transcription and replication through regulation of RNA polymerase II activity and or post-transcriptional mechanisms. Full article

White Striping (WS) is a macroscopic defect of the pectoralis major muscle, characterized by distinct white striations that impair meat acceptability and commercial value. It is a phenotype with polygenic inheritance, controlled by several QTLs and genes associated with muscle repair and metabolism. Beyond genetic factors, phenotypic manifestation is strongly modulated by the environment. This review integrates research on genetic predispositions and modulating factors to provide a holistic overview of WS in broilers. The defect predominantly affects heavier birds with high breast yield and elevated ultimate breast pH. LRSAM1 gene, on chromosome GGA17, is identified as a putative candidate gene as its expression co-localizes with the phenotypic QTL. Chromosome GGA5 has recently been identified as the primary genomic region of interest hosting a cluster of specific markers. Research on dietary strategies has extensively explored the manipulation of feed formulations, especially of amino acids. While results for some nutrients like methionine remain conflicting, restricting lysine during the growth phase could be an effective dietary intervention for reducing WS severity. Management offers the most practical short-term solutions, whereas selective breeding enables meaningful and permanent progress across generations, given the moderate heritability of many quality-related traits. Effective mitigation requires an integrated approach combining welfare, environmental control, and precision feeding throughout the production cycle, while acknowledging trade-offs with productivity. To meet evolving consumer expectations, the industry must embrace practices that are simultaneously scientifically rigorous, ethically responsible, and environmentally sustainable. Full article

Background/Objectives: Necrotic enteritis (NE), induced by Clostridium perfringens, is responsible for significant economic losses in the poultry industry worldwide. The growing restrictions on antibiotic use have driven the search for alternative strategies for disease control. The purpose of this study is to isolate and characterize lytic phages targeting multidrug-resistant C. perfringens type G recovered from chickens with NE. Methods: C. perfringens was isolated from chickens with NE using a culture method with selective TSC agar. Bacterial identification was carried out using biochemical tests and PCR. C. perfringens isolates were toxinotyped by PCR. Antibiotic susceptibility test was performed using the agar dilution method. Bacteriophages were isolated from chicken intestine samples collected from wet markets using the double-layer agar technique. Phage isolates were characterized by host range, one-step growth, stability, and whole genome sequencing. The efficacy of phage CPP8 in controlling multidrug-resistant C. perfringens type G was evaluated in GAM broth. Results: In this study, 16 C. perfringens strains were isolated from 100 chickens suspected of NE. Among these isolates, 10 (62.5%) belonged to type G, while the remaining 6 (37.5%) were type A. A total of 11 phages capable of lysing C. perfringens type G were isolated from the chicken intestine. Among them, phage CPP8 has the widest host range, short latent period, large burst size, and high stability. Moreover, the genome of CPP8 lacked genes related to antibiotic resistance, toxins, virulence factors, or lysogeny. Treatment with CPP8 resulted in a significant reduction in viable counts of C. perfringens at 37 °C. Conclusions: Our findings highlight phage CPP8 as a promising candidate for bio-control of multidrug-resistant C. perfringens type G. Full article

Clear cell renal cell carcinoma (ccRCC) is characterized by marked biological heterogeneity, which limits the prognostic accuracy of conventional clinicopathological models. Increasing attention has therefore focused on identification of biomarkers that can enhance risk stratification throughout all stages of the disease. Starting from the current state of the art, this narrative review summarizes and critically appraises the evidence published over the past decade regarding prognostic biomarkers in ccRCC. The analysis is structured into four overarching domains: (i) genomic biomarkers, covering somatic alterations and transcriptomic signatures; (ii) tissue-based biomarkers, including immunohistochemical surrogates and immune microenvironment features; (iii) circulating biomarkers, such as systemic inflammation parameters and indices; and (iv) integrated predictive models, represented by emerging multi-omic approaches. Going through the broad framework of potential prognostic biomarkers, emphasis is placed on their individual and integrative value in relation to classic clinical-pathological factors and survival parameters. At the tissue level, chromosome 3p-related alterations constitute a central molecular feature of ccRCC. Among these, BAP1 loss has emerged as one of the most consistently validated indicators of aggressive tumor behavior. Disruption of the SETD2/H3K36me3 axis and immune-related biomarkers, including PD-L1 expression, have demonstrated prognostic associations in selected settings, although with variable and context-dependent performance. In the circulating compartment, plasma KIM-1 has shown prognostic relevance following nephrectomy, while postoperative detection of circulating tumor DNA (ctDNA) may identify patients at increased risk of recurrence. However, limited analytical sensitivity and methodological heterogeneity currently restrict the broader clinical applicability of ctDNA-based strategies. Systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio, show reproducible associations with outcomes but largely reflect host inflammatory status rather than tumor-specific biology. However, no single biomarker currently supports routine prognostic implementation in ccRCC. Future progress will likely depend on integrative models combining genomic, tissue-based, immune, and circulating parameters with established clinical variables. Prospective validation and clear demonstration of incremental clinical utility will be essential before such strategies can meaningfully inform therapeutic decision-making. Full article

Deep-seated landslide complexes are widespread in soft-rock hill-country landscapes, yet their regional morphometric organisation and controlling factors remain insufficiently quantified. This study uses high-resolution (1 m) airborne LiDAR-derived terrain data integrated with geological and drainage-network datasets to investigate landslide complexes in the eastern Tararua District, New Zealand. A relative, unit-based morphometric framework is applied to compare terrain derivatives (including slope, aspect, and multi-scale relative relief) between mapped landslides and their host geological units. To isolate intrinsic lithological controls from geomorphic influences, the analysis is restricted to landslides occurring entirely within a single geological unit. The results indicate that lithology exerts first-order control on landslide morphometry, while fluvial incision and valley confinement regulate landslide initiation and persistence. Landslides are preferentially associated with low- to mid-order channels, indicating strong hillslope–channel coupling within a young, actively uplifting landscape. A conceptual threshold framework is proposed, showing that landslides develop where lithological susceptibility and relief amplification jointly exceed stability thresholds. By integrating geological information with LiDAR-based morphometric analysis, this study provides a transferable framework for distinguishing instability regimes and improving understanding of sediment dynamics and landscape evolution in soft-rock terrains. 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