Search Results (439)

Natural Ophiocordyceps sinensis is a highly valued medicinal fungus known for its antitumor, immunomodulatory, and antiviral properties. Due to extensive overharvesting in Asia, cultivated alternatives have become increasingly important. This study aimed to evaluate the biological activity and chemical composition of extracts obtained from cultivated Ophiocordyceps sinensis grown using different rice substrates. Methanolic extracts were prepared from solid-state cultivated Ophiocordyceps sinensis grown on Oryza sativa var. indica and Oryza sativa var. japonica. Antioxidant activity was determined using the DPPH assay, while proteolytic activity was evaluated with the azocasein substrate. Chemical characterization of major compounds was performed using ¹D and ²D NMR spectroscopy, together with IR spectroscopy. UV/Vis spectrophotometry was employed to confirm the formation of silver nanoparticles in AgNO₃ solution. Antimicrobial activity was tested against bacterial strains, including Escherichia coli and Staphylococcus aureus. All prepared methanolic extracts exhibited measurable antioxidant and proteolytic activities. The dominant identified compounds were Z-oleic acid, linoleic acid, and D-mannitol. Selected extracts successfully induced the formation of silver nanoparticles. The highest antimicrobial activity against Escherichia coli was observed for sample 1OS, reaching a mean % RIZD value of 129.32 ± 0.58%. Full article

Dengue virus (DENV) and chikungunya virus (CHIKV) co-circulate in many regions and present with overlapping clinical features, which complicate accurate diagnosis and disease management. This study develops an integrative transcriptomic framework to identify robust host gene signatures that distinguish between dengue, chikungunya, and healthy states. Publicly available RNA sequencing (RNA-seq) datasets derived from human blood samples were analyzed using a cross-validation design to ensure robustness and prevent information leakage. Differential expression analysis was performed independently within each dataset using the Generalized Linear Models with Quasi-Likelihood F-tests and Magnitude–Altitude Scoring (GLMQL-MAS) framework, followed by Cross-Magnitude–Altitude Scoring (Cross-MAS) integration to identify shared and virus-specific gene signatures. A strict consensus approach across folds was applied to derive reproducible gene sets. These signatures were used for dimensionality reduction and multinomial logistic regression to evaluate classification performance. A small subset of selected genes showed strong discriminative performance within the cross-validation framework, with test balanced accuracy reaching 0.97, which improved upon models using all genes. Biologically, both infections exhibited a shared antiviral response characterized by interferon signaling and innate immune activation. However, distinct virus-specific patterns were identified. Dengue infection was associated with cell-cycle and DNA replication pathways, while chikungunya infection showed stronger enrichment of inflammatory and immune signaling pathways, including NF-kappaB and Toll-like receptor signaling. Overall, this study provides a cross-validation-based framework for integrative transcriptomic analysis and identifies compact, reproducible host-response signatures with strong discriminative signals in the analyzed cohorts. These signatures require validation in larger independent cohorts before any clinical or diagnostic application. Full article

Interferons (IFNs) are antiviral cytokines that serve as key mediators of the innate immune response, and their production is induced in the majority of cells within hours of pathogen entry. IFNs are predominantly produced by pathogen-infected cells; however, their antiviral effects extend to surrounding cells through autocrine and paracrine signaling mechanisms, inducing the transcription of hundreds of antiviral genes. Numerous gene products either interfere directly with viral replication or play regulatory roles that influence the progression and strength of the ensuing immune response. Viruses, on the other hand, have devised techniques to circumvent the host antiviral immune response and establish infection. This review focuses on the current state of evidence demonstrating how certain viral proteins block antiviral responses via immunomodulatory strategies and discusses how to overcome these immune evasion tactics. Full article

Background: Hepatitis C virus (HCV) remains a major cause of preventable liver-related mortality in the United States despite highly effective direct-acting antivirals (DAAs). Contemporary assessment of mortality trends and disparities is essential for elimination efforts. Methods: Using CDC WONDER multiple cause-of-death data (1999–2023), we identified HCV-related deaths using ICD-10 codes for acute and chronic HCV (B17.1, B18.2) and calculated age-adjusted mortality rates (AAMRs) per 100,000 (2000 US standard). Rates were stratified by sex, race/ethnicity, census region, and 2013 NCHS urban–rural classification. Joinpoint regression quantified temporal inflection points and annual percent changes (APCs). Results: Overall HCV-related AAMR increased from 1.8 (1999) to a peak of 5.0 (2014), then declined to 2.3 (2023), with a marked post-2014 decrease (APC −8.2%). Mortality was consistently higher in males than females (2023 rate ratio 2.57). In 2023, American Indian/Alaska Native individuals had the highest mortality (AAMR 8.7; rate ratio 3.48 vs. non-Hispanic White), followed by non-Hispanic Black individuals (AAMR 6.2; rate ratio 2.48). Mortality remained highest in the West and was higher in non-metropolitan than metropolitan counties (AAMR 2.8 vs. 2.3; rate ratio 1.22), with a slower post-2014 decline in non-metropolitan areas. Conclusions: Our findings indicate that while the DAA era has been associated with a substantial reduction in HCV-related mortality at the national level, this progress has not been uniform across all populations. Persistent excess mortality among Native American and non-Hispanic Black individuals may reflect inequities in the HCV care cascade, including screening, confirmatory testing, linkage to specialty care, insurance-related restrictions, and the high cost of antiviral therapy. These results highlight the need for policies and public health strategies that improve equitable and affordable access to curative HCV treatment. Full article

Chlorine dioxide (ClO₂) is a neutral oxidant molecule with a short lifespan once in contact with electron donors (organic matter). ClO₂ solutions have antiviral, antibacterial, antifungal, anti-protozoan, anti-inflammatory, anticancer, and wound-healing activity and it was used at safe concentrations on patients from different countries during the COVID-19 pandemic. In Mexico, 1067 COVID-19 patients received compassionate treatments with ClO₂ during the 2020/2021 pandemic years. We describe the treatments and clinical reports of these patients, as it concerns the oxygen saturation (SpO₂) recovery, and provide a biochemical explanation. The number of healed patients was 1057, >99% of the total and SpO₂ showed a hyperbolic fast increase. This might happen because ClO₂ attracts one electron from the organic matter and produces a chlorite anion (${\mathrm{ClO}}_2^{-}$). This new molecule is known to exhibit metabolic activity in the blood stream. On the one hand, it will perform the aforementioned antibiotic and healing properties. On the other hand, it will also allow the production of oxygen (O₂) to be transported by the Oxyhemoglobin. This reaction is mediated by an intermediate state of a ferryl molecule (Fe=O) in the allosteric heme site of methemoglobin, which behaves as a reductase enzyme. This reaction can explain the rapid and steady increase in O₂ saturation in healed patients. 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

Functional antibody-dependent enhancement (ADE) represents a fundamental and context-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both the neutralization and Fc receptor-dependent enhancement of infection. In flavivirus research, this duality complicates the interpretation of conventional serological metrics and limits the reliability of single-parameter correlates of immunity, particularly in populations with complex exposure histories. Over the past decade, functional ADE assays have evolved from specialized mechanistic tools into integrated immune assessment platforms supporting translational immunology, vaccine evaluation, and population-level immune surveillance. These platforms incorporate Fcγ receptor-relevant target cell systems, standardized viral inputs, dilution series-based profiling, quantitative enhancement metrics, and structured quality control frameworks to enable reproducible, comparable, and context-aware functional measurements across cohorts and laboratories. A central concept emerging from these developments is that ADE reflects a dynamic functional immune state rather than an intrinsic property of antibodies or a direct indicator of pathological risk. Accordingly, functional ADE platforms support the contextual interpretation of antibody activity across physiologically relevant conditions, facilitating discrimination between transient functional enhancement and clinically meaningful immunological risk. By integrating functional ADE metrics with serological, cellular, and epidemiological data, these platforms provide a structured framework for interpreting immune profiles in vaccine evaluation, booster strategy design, and population-level risk stratification. This review synthesizes the development, standardization, and global dissemination of functional ADE platforms and discusses key principles governing biological relevance, analytical robustness, and inter-site transferability. Emerging directions integrating functional ADE profiling with systems immunology, immunogenomics, and computational modeling are highlighted as pathways toward predictive, decision-support-oriented frameworks. By positioning ADE platforms as immune assessment infrastructures rather than isolated assays, this review underscores their value for mechanistic inquiry, translational interpretation, and preparedness-oriented responses to emerging viral threats in the absence of definitive correlates of protection. Full article

Clinically robust molecular biomarkers for depression have remained elusive, despite extensive transcriptomic research. This gap is consequential: depression is prevalent and heterogeneous, yet objective measures to quantify burden, stratify patients, and track recovery remain limited. Here, we review evidence that intron retention (IR) can serve as a homeostatic state variable—and therefore a sensitive biomarker—reporting stress adaptation and recovery at an upstream regulatory layer, often preceding or outperforming differential gene expression (DEG) readouts. Mechanistically, IR enables bidirectional fine-tuning of effective gene output: increased IR (IncIR) can throttle output under overload, whereas decreased IR (DecIR) releases this brake to restore gene output. Because these shifts are reversible and treatment-responsive, IR signatures can function not only as disease markers but also as pharmacodynamic metrics for blood-based monitoring of drug response and recovery. To evaluate the clinical utility of IR, we use depression as a proof of concept and focus on two interventions: (i) the Kampo formula hangekobokuto (HKT), which is associated with IR normalization consistent with reduced peripheral inflammatory load; and (ii) ketamine, where IR patterns measured before ketamine treatment in non-responders are linked to stronger innate-immune/antiviral activity, suggesting a higher inflammatory load that may limit treatment benefit. Finally, we discuss transdiagnostic extensions beyond depression, using early cognitive decline (mild cognitive impairment, MCI) as a stringent, biologically distal test case for blood-based IR/DI readouts and motivating independent cohort replication and longitudinal validation. Full article

Located on the traditional and ancestral homelands of the Arapaho, Cheyenne, and Ute Nations, Colorado State University’s Mountain Campus hosted the 25th Annual Rocky Mountain Virology Association meeting. The three-day event, held from 26 September to 28 September 2025, welcomed 152 participants focused on the following topics: viruses, prions, immunology, transmission, structural biology, and vector biology. This year’s Randall Jay Cohrs Keynote Presentation summarized ongoing research on viral glycoproteins in relation to viral entry and assembly. Understanding the role of viral glycoproteins is essential in vaccine and antiviral development for enveloped RNA viruses. Alongside rigorous scientific discourse and networking, attendees made the most of their time by hiking amidst beautiful fall colors, wildlife, and young aspens starting the forest anew. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations from the 25th annual meeting. Full article

Viral infections remain a global public health challenge. Stimulating the innate immune system is a potent therapeutic strategy that promotes pathogen clearance, directly impacting disease severity and clinical outcomes. Interferons and interferon-stimulated genes (ISGs) are critical components of this antiviral defense system. Neomycin, an aminoglycoside antibiotic, can induce ISG expression and help establish an antiviral state. In this study, we demonstrated that neomycin induces the production of pro-inflammatory cytokines (IL1β, TNFα, IL6, GM-CSF, and IFN-γ) in peripheral mononuclear blood cells (PBMCs) and activates key antiviral ISGs, including MxA, OAS1, and IRF7. The protein expression profiles elicited by neomycin were comparable to those induced by poly(I:C). Intranasal delivery of neomycin to CBA and BALB/c mice induced various ISGs in both the respiratory tract and splenic tissues. Prophylactic administration of neomycin significantly inhibited influenza B virus replication in the lung and nasal turbinates of CBA mice in a sublethal infection model. Overall, our data suggest that neomycin, when used prophylactically alone or combined with other antiviral strategies, shows considerable potential for the attenuation of influenza B virus infections. Full article

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization in infancy. Reliable biomarkers reflecting host antiviral responses and disease dynamics are still lacking. Methods: We evaluated the expression of the interferon-stimulated genes IFI44L, IFI27, and RSAD2 in peripheral blood of infants hospitalized with RSV bronchiolitis at admission and discharge, and in healthy controls, using multiplex RT-qPCR. A composite interferon-based Viral Score was derived from coordinated ISG expression. Results: All three ISGs and the Viral Score were markedly elevated during acute RSV infection at hospital admission compared with discharge and healthy controls. Following clinical recovery, ISG expression and Viral Score declined significantly and approached baseline levels. The Viral Score clearly discriminated acute infection from recovery and healthy states, reflecting dynamic systemic interferon activation. Conclusions: A Viral Score based on IFI44L, IFI27, and RSAD2 captures systemic antiviral immune responses in infants with RSV bronchiolitis and declines with disease resolution. This interferon-based host-response signature represents a promising biomarker for defining viral infection status and monitoring disease dynamics in pediatric respiratory infections. Full article

Pregnancy represents a distinct immunological and physiological state that modifies maternal susceptibility to SARS-CoV-2 and influences the clinical and biological course of COVID-19. Accumulating evidence indicates that the interaction between viral entry determinants, gestation-specific immune modulation, placental endocrine–angiogenic pathways, and systemic inflammatory responses underlies the characteristic manifestations of SARS-CoV-2 infection during pregnancy. This review consolidates current understanding of SARS-CoV-2 viral structure, receptor biology, and the gestational regulation of key entry cofactors, including ACE2, TMPRSS2, NRP1, CTSL and FURIN, within reproductive and placental tissues. The review further integrates documented mechanisms of cytokine-mediated immune dysregulation, endothelial injury, thrombo-inflammation, and steroidogenic alteration observed in affected pregnancies, and examines their contribution to placental malperfusion, preeclampsia-like presentations, fetal growth abnormalities and preterm birth. Published molecular and computational studies characterising trophoblast antiviral defenses, receptor expression patterns, and structural determinants of Spike–ACE2 affinity are synthesised to contextualise the biological basis of placental susceptibility and the rarity of confirmed transplacental transmission. Current evidence on maternal clinical outcomes, fetal and neonatal consequences, vaccination efficacy, therapeutic considerations and contemporary management guidelines is also critically reviewed. By integrating molecular, immunological, pathological and clinical insights, this article provides a comprehensive framework for understanding the interaction between SARS-CoV-2 infection and pregnancy-specific physiology, with implications for risk assessment, preventive strategies and maternal–fetal care. Full article

Parainfluenza virus 5 (PIV5) can establish persistent infections in host cells despite encountering innate immune defenses, including the complement (C′) system. The host determinants that enable persistently infected cells (PI) to evade C’-mediated clearance remain largely undefined. Here, we identify the mitochondrial antiviral signaling (MAVS) protein, a central adaptor in double-stranded RNA-triggered antiviral and pro-survival signaling pathways, as a critical mediator of both PIV5 persistence and acquired resistance to C’ lysis. Wild-type (WT) PIV5-infected A549 cells were initially sensitive to C’-directed killing, but these cells rapidly establish a PI in culture with ~25% of the cell population becoming resistant to C’ lysis by day 2 and ~75% by day 4. In contrast, PIV5-infected A549 MAVS-deficient (MAVS KO) cells exhibited elevated viral gene expression, increased deposition of C3 and the membrane attack complex, and were more susceptible than WT cells to C′ killing. PIV5-infected MAVS KO cells showed rapid cytopathic effects and never established a stable PI. While pharmacological suppression of viral gene expression with ribavirin (RBV) restored the survival of PIV5-infected MAVS KO cells into a long-term PI-like state, these RBV-induced PI cells remained sensitive to C’ lysis. Collectively, these findings demonstrate a role of MAVS in modulating a PIV5 infection in culture, to facilitate both the conversion of a PIV5 acute infection to a PI and development of resistance to C’ killing. Full article

Type I interferons (IFN-I) are pleiotropic cytokines best known for their antiviral impacts. However, they are known to also impact immune responses outside of viral infection through directly signaling many populations of innate and adaptive immune cells. Here, we focus on the complex body of findings from viral, bacterial, and parasitic infection models, cancer and autoimmunity studies, as well as in vitro experiments using human and murine T cells, demonstrating that IFN-I can be directly sensed by CD4 T cells. Such signaling has been shown to influence many central aspects of antigen-specific CD4 T cell responses, including proliferation, apoptosis, effector subset differentiation, and memory formation. These effects are frequently divergent and sometimes opposing, likely reflecting how differences in variables related to the IFN-I signal, overall inflammatory milieu, and the CD4 T cell integrate to shape outcomes. Indeed, we discuss findings supporting a framework in which dynamic engagement of canonical and non-canonical signaling pathways downstream of IFN-I, which are contingent on a cell’s activation state, play a key role in determining whether and how IFN-I promotes, restrains, or otherwise reprograms CD4 T cell fates. Together, these observations highlight the impressive scope of regulation that IFN-I signals to CD4 T cells can exert, parallel to its actions on other immune and non-immune cell types. They also suggest that harnessing such signaling could offer powerful therapeutic strategies to shape CD4 T cell immunity in diverse context-dependent situations. Full article

The human metapneumovirus (HMPV) Fusion (F) glycoprotein is a high-priority target for “fusion-locking” agents that stabilize its metastable prefusion state. While monomeric catechins like EGCG are known antivirals, the molecular basis for the superior activity of structurally complex dimeric catechins remains poorly understood. We employed an advanced biophysical workflow, integrating 100 ns all-atom molecular dynamics (MD), free energy landscape (FEL) analysis, and MM/GBSA thermodynamic integration to decode the Structure–Dynamics Relationship (SDR) of 210 Camellia sinensis (Green tea) phytochemicals. The results reveal a “Galloylation-Driven Anchoring” mechanism: the galloyl moiety of prodelphinidin A2 3′-gallate provides critical electrostatic complementarity to the Asp325-Asp336 acidic ridge. FEL analysis quantitatively demonstrates that this anchoring leads to pronounced stabilization of the F protein in a deep, kinetically favored global minimum (ΔG = 9.357 kJ/mol), effectively raising the energy barrier for the fusogenic conformational shift. This study provides a comparative and mechanistically informed computational proof-of-concept for the use of dimeric natural scaffolds as precision fusion-locking agents, offering a roadmap for experimental biophysical validation. In this workflow, molecular docking was employed exclusively as a qualitative structure-based filtering step, while all quantitative conclusions regarding stabilization and binding energetics were derived from post-docking MD, FEL, and MM/GBSA analyses. Full article