Search Results (3,044)

Cathepsin C (CTSC) is a major lysosomal cysteine protease characterized by its involvement in multiple essential pathological processes associated with various viral infections and pathogenesis, such as influenza virus and coronavirus. However, the antiviral spectrum of CTSC and the molecular mechanisms underlying its activity remain to be fully elucidated. In this study, we demonstrate that CTSC significantly inhibits the infection of influenza A virus (IAV) H1N1 both in vitro and in vivo. Mechanistically, the antiviral function of CTSC is associated with attenuation of the PI3K-AKT signaling pathway, thereby inducing cell apoptosis and reducing inflammation, which ultimately limits the virus’s ability to hijack host resources. Taken together, our findings highlight the crucial role of CTSC in defense against H1N1 by targeting PI3K-AKT pathway and suggest a prospective antiviral target against the infection of H1N1. Full article

Background/Objectives: Immunodeficiency can be induced by a variety of factors, such as aging, stress and poor nutrition, and leads to increased susceptibility to infection and disease. The current research was conducted to determine the immunoenhancing potential of yam and its underlying mechanism in a murine model of cyclophosphamide (CTX)-induced immunosuppression. Methods: The gut microbial community and generation of short-chain fatty acids (SCFAs) in response to yam were analyzed by 16S rRNA sequencing and GC-MS. The immune cells in the spleen were analyzed using flow cytometry. GPR41/GPR43/GPR109A triple-knockout mice were used to demonstrate the critical involvement of SCFAs in mediating the protective effect of yam, and RNA-sequencing technology was applied to investigate the potential mechanism by which yam orchestrated the observed metabolic, immune and reparative responses. Results: Yam alleviated the decline in spleen and thymus indices and modulated the frequency of B cells and CD4⁺ and CD8⁺ T cells and promoted the production of IgA, IgG and IgM. Yam increased the secretion of cytokines in the intestine and upregulated the levels of claudin and ZO-1. Yam also increased the content of SCFAs and induced beneficial modifications to the gut microbiota composition. The immune-enhancing activity of yam was confirmed, as evidenced by a notable decrease in viral load in immunosuppressed mice inoculated with influenza virus and its capacity to mitigate inflammatory response in pulmonary tissues. Conclusions: This study suggests that yam enhances immunity by synergistically regulating the gut–immune axis, supporting its development as a functional food intervention in managing immunodeficiency conditions. Full article

Background/Objectives: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus type 3 (PIV3) are leading causes of acute respiratory infections in children and the elderly, yet no licensed T-cell vaccines are available. This study aimed to develop multivalent T-cell vaccine candidates against these pathogens using a live attenuated influenza virus (LAIV) vector platform. Methods: Conserved F, N, and M proteins of RSV, hMPV, and PIV3 were identified through multiple sequence alignments. Fragments enriched with experimentally confirmed and predicted T-cell epitopes were selected using the IEDB and NetMHCpan servers. These fragments were assembled into polyepitope immunogenic cassettes, and their selected order was determined by thermodynamic analysis of mRNA secondary structures using the RNAfold Web Server. The selected cassettes were cloned into the neuraminidase (NA) gene of a cold-adapted LAIV vector. Recombinant viruses were rescued by reverse genetics and assessed for replicative fitness in embryonated chicken eggs and MDCK cells, NA enzymatic activity and genetic stability upon serial passaging. Results: Four cassettes were designed for RSV, three for hMPV, and one for PIV3, all containing fragments with multiple T-cell epitopes. Three recombinant viruses of LAIV/RSV type and three of LAIV/hMPV type were successfully rescued, while attempts to recover the remaining recombinant viruses, i.e., LAIV/RSV and LAIV/PIV3, were not successful. All rescued recombinant viruses replicated to titers comparable to the parental LAIV strain and retained the full-length insert for at least eight passages in eggs. Importantly, NA enzymatic activity of the LAIV vector was not compromised by the insertion of the polyepitope T-cell cassettes. Conclusions: We developed a panel of recombinant T cell-based vaccine candidates against RSV and hMPV using the LAIV vector platform. These recombinant viruses encode conserved T-cell epitopes of the target viruses while retaining the biological properties of LAIV strains. Taken together, these characteristics warrant further evaluation of these recombinant viruses in appropriate relevant in vitro models to directly assess their immunogenicity in terms of stimulating a T-cell response against target pathogens. Full article

This review aims to examine the immunological, anti-inflammatory, antiviral, and antibacterial activities of key whey and milk proteins, specifically lactoferrin, glycomacropeptide, β-lactoglobulin, α-lactalbumin and their derived peptides, particularly lactoferricin and lactoferrampin, highlighting their potential as preventive or therapeutic agents. Whey and dairy products represent complex biological matrices that, beyond their high nutritional value, serve as reservoirs of bioactive proteins and peptides with documented health-promoting properties. It has been reported that certain whey proteins (WPs) and whey-derived peptides may contribute to improvements in both innate and adaptive immunity, exert direct antiviral and antibacterial effects while also modulating host defenses through immunoregulatory, antioxidant, and anti-inflammatory activities. These mechanisms contribute not only to enhanced resistance against viral pathogens but also to maintaining intestinal homeostasis and microbiota balance, both of which are critical during infection. In recent years, particularly in the context of the COVID-19 pandemic, natural bioactive compounds derived from whey, and, more broadly, milk, have attracted increasing attention as potential adjuncts or alternatives to conventional antivirals, with reported activity not only against SARS-CoV-2, influenza but also other viral and microbial infections. Despite encouraging in vitro and in vivo evidence, clinical validation remains limited, and the antiviral and immunomodulatory effects of WPs still require deeper mechanistic clarification. Future research should focus on identifying molecular targets, as well as characterizing the pharmacokinetics and safety profiles of WPs and WP peptides across diverse clinical settings. At the same time, attention should be given to optimizing their application as nutraceuticals or functional dairy ingredients. Full article

The concurrent circulation of SARS-CoV-2 and influenza presents a complex immunological landscape. While biological evidence suggests that prior or current infection with one virus can alter susceptibility to the other, conventional epidemiological models often obscure these effects by aggregating co-infected populations into a single compartment. This structural simplification limits our ability to quantify how infection history shapes population-level transmission dynamics. We developed a stratified, deterministic co-infection model that explicitly distinguishes between single, concurrent, and sequential infections by accounting for sequence-dependent heterogeneity in susceptibility and transmissibility. Our primary innovation is a transmission source–pathway decomposition framework that mathematically attributes the rate of new infections to its specific transmission source (i.e., which infectious subpopulation is generating the transmission: the singly-infected, co-infected, or sequentially-infected class) and transmission pathway (i.e., which susceptibility class is receiving new infections: fully susceptible individuals, or those with prior immunity, or those with active co-infection). This framework accounts for altered susceptibility and transmissibility dependent on infection history. Our model-based analysis reveals a profound, sequence-driven asymmetry in transmission. In a baseline co-epidemic scenario, COVID-19 is predominantly driven by a sequential source: individuals who contracted COVID-19 after recovering from influenza are estimated to account for approximately 73% of new COVID-19 cases and approximately 76% of the disease burden, as predicted by our model. Conversely, influenza transmission remains driven by singly infected individuals (approximately 96% of new influenza cases inferred using our model). This sequence-driven asymmetry was robust to changes in model structure (especially, the inclusion of an influenza latent period in a sensitivity analysis) and across scenarios of varying relative transmissibility for the two viruses. Interventions exhibit pathway-specific effects: COVID-19 vaccination, for instance, disproportionately disrupts this dominant sequential transmission engine by protecting the most immunologically vulnerable hosts. Our model-based findings suggest that infection history may be a primary driver of co-epidemic dynamics. Our framework reveals a plausible, asymmetric interaction where an initial influenza wave can fundamentally reshape the transmission landscape for COVID-19, and demonstrates how a prior COVID-19 wave may fuel subsequent influenza transmission under specific temporal conditions. These findings generate the testable hypothesis that cross-viral susceptibility is a key control point and underscore the importance of pathway-aware intervention strategies that account for infection history. Full article

Influenza D virus (IDV) is a respiratory pathogen affecting the health of cattle, thereby causing economic losses. This study was conducted to detect and isolate IDV, investigate its molecular characteristics, and examine the antibody response to IDV in naturally infected cattle. Real-time RT-PCR was used to analyse 279 nasal swabs and blood sera collected from cattle on farms in the Thrace district of Türkiye, bordering the European Union, for IDV-RNA. One sample from 2020 from a small, family-owned farm (D/OK lineage), two samples from 2021 from an integrated farm (D/OK lineage), and two samples from 2024 (D/Yama2019) from an integrated farm were found to be positive for IDV-RNA. All five samples were collected from farms located in Kırklareli. Positive samples were subjected to virus isolation and phylogenetic analyses. Serum samples were analysed using ELISA and HI tests. Of the 279 samples collected, 1.79% tested positive for IDV-RNA in real-time RT-PCR. Seroprevalence, measured for the first time in Türkiye, was found to be 45.5% and 55.19% by ELISA and HI tests, respectively. Key factors statistically associated with IDV seropositivity included the study year, geographical location, and farm type. Clinically, nasal discharge and cough were the primary symptoms in seropositive animals. Genetic analysis revealed that the 2020–2021 samples clustered within the D/OK lineage, while the 2024 samples belonged to the D/Yama2019 lineage. The findings suggest the co-circulation of multiple IDV strains, although this should be interpreted cautiously given the limited number of sequences in the Thrace region. Considering the lack of an influenza D virus (IDV) vaccine, these findings emphasise the importance of continued surveillance and diagnostic testing of cattle to limit viral spread, protect cattle health, and reduce economic losses associated with IDV. Full article

Background/Objectives: We report a case of severe dermatomyositis demonstrating characteristic widespread extraosseous uptake on ^99mTc-methylene diphosphonate (^99mTc-MDP) bone scintigraphy. This study highlights the diagnostic value of this modality in detecting active inflammatory myopathy when conventional muscle biopsy is inconclusive and introduces its novel use for intraoperative gamma-probe-guided biopsy to precisely target metabolically active muscle. This approach may help target metabolically active muscle in heterogeneous idiopathic inflammatory myopathies (IIMs). Case Presentation: A 49-year-old man developed progressive proximal muscle weakness (Medical Research Council grade 2/5 proximally, 5/5 distally) beginning in June 2025 following influenza infection, accompanied by dysphagia, classic dermatomyositis cutaneous manifestations, back pain, and difficulty standing. Laboratory evaluation revealed elevated inflammatory markers (ESR 55 mm/hr, CRP 20 mg/L), leukocytosis (16.58 × 10⁹/L), markedly raised creatine kinase (19,937 IU/L), and troponin T levels. An initial quadriceps muscle biopsy performed on 29 July 2025 was non-diagnostic. Three-phase ^99mTc-MDP scintigraphy (~1110 MBq) demonstrated intense, diffuse extraosseous uptake involving bilateral deltoids (symmetric), biceps and triceps (patchy), paraspinal muscles (longitudinal), gluteal muscles, thighs (quadriceps and hamstrings), and gastrocnemius muscles, with relative suppression of appendicular skeletal uptake on delayed images due to soft-tissue tracer dominance—findings consistent with severe inflammatory myopathy. Following reinjection (~1100 MBq), intraoperative gamma-probe-guided biopsy targeted areas of highest uptake (left quadriceps femoris and distal triceps brachii; intraoperative counts 1300–1400 versus background ~500). Histopathology revealed histiocyte-predominant inflammation with myofibre necrosis and regeneration, sparse CD4⁺ T-cell infiltrates, and absence of fibrosis, consistent with necrotising myopathy. Positive antinuclear antibodies and strong anti-Mi-2 antibodies confirmed the diagnosis of dermatomyositis. Treatment included pulse methylprednisolone followed by oral prednisone taper, methotrexate, azathioprine, intravenous immunoglobulin, and planned rituximab therapy. Discussion: Whole-body ^99mTc-MDP scintigraphy provided a complementary whole-body functional assessment of disease extent, revealing widespread muscular involvement. The novel application of intraoperative gamma-probe-guided biopsy enabled real-time targeting of metabolically active muscle, facilitating targeted sampling after an initial non-diagnostic biopsy and yielding supportive histopathological findings. This dual diagnostic and interventional role demonstrates the technical feasibility of gamma-probe guidance in a diagnostically challenging case of dermatomyositis. Conclusions: In our case, the integration of ^99mTc-MDP scintigraphy with gamma-probe-guided biopsy enabled precise targeting of metabolically active muscle following an initial non-diagnostic biopsy. This multimodal approach may be useful in selected diagnostically challenging cases of severe inflammatory myopathy. Larger studies are needed to evaluate its reproducibility and added value. Full article

Background/Objectives: Upper respiratory tract infections (URTIs), including common cold and influenza, remain a major global health burden, and their symptomatic management often includes the use of herbal medicines alongside conventional therapies. The aim of this study was to evaluate the real-world use of herbal medicines as drug candidates in the management of URTIs in Estonia, with a focus on differences between pharmacy customers and pharmacy professionals. Methods: A cross-sectional survey was conducted among 905 participants, including 400 pharmacy customers and 505 pharmacy professionals (pharmacists and pharmacy assistants). Standardized questionnaires were used to assess the frequency of use, perceived effectiveness, and safety considerations of commonly used herbal substances and home remedies in adults and children. Results: Herbal medicines and home remedies were widely used, reported by 68% (95% CI: 63.4–72.6%) of pharmacy customers and 71% (95% CI: 67.0–75.0%) of pharmacy professionals. The most commonly used herbal substances included lemon (79%), ginger (57%), garlic (56%), raspberry (55%), and chamomile (50%). While most respondents perceived these remedies as effective for symptom relief, notable discrepancies were observed between customer and professional assessments of efficacy. The use of several herbal substances in children did not consistently align with European Medicines Agency recommendations, highlighting potential safety concerns. The findings demonstrate that widely used herbal substances represent real-world candidates for supportive URTI management; however, their perceived effectiveness and patterns of use are not always supported by regulatory guidance or clinical evidence. These results underscore the need for further pharmacological and clinical studies, as well as improved evidence-based communication between healthcare professionals and patients. Conclusions: The results allow the identification and prioritization of herbal substances as real-world drug candidates for further pharmacological and clinical development. Full article

To address the lack of a commercially available vaccine for goose circovirus (GoCV), we developed and evaluated a prokaryotically expressed subunit vaccine targeting the viral capsid (Cap) protein. A truncated Cap protein (GoCV-ΔCap) was expressed in Escherichia coli (E. coli) and formulated with aluminum hydroxide as a subunit vaccine (GoCVsubvac). Goslings were primed intramuscularly (i.m.) with high (75 µg) or low (15 µg) doses GoCVsubvac, followed by a boost 14 days later. At 14 days post-boost, goslings were challenged with GoCV and were administered a bivalent inactivated vaccine against Newcastle disease virus (NDV) and H9-subtype Avian influenza virus (AIV). Using our established gosling pathogenicity model, vaccine efficacy was evaluated via body weight, lesions, viral load, antibody titers, cytokine responses, and interference with NDV/AIV immunity. Results demonstrated that the GoCV-ΔCap vaccine, especially the high-dose formulation, provided effective immunoprotection. It elicited robust humoral and cellular immune responses, reduced lymphoid pathology, and decreased the viral detection rate in lymphoid tissues from 100% (5/5) in infected controls to 40% (2/5). Importantly, it alleviated GoCV-induced immunosuppression and preserved the immunogenicity of co-administered vaccines. This novel subunit vaccine is a promising candidate for controlling GoCV disease (GoCVD). Full article

Influenza is an acute viral respiratory infection that generates a substantial clinical and socioeconomic burden, especially among high-risk populations such as older adults. In Spain, influenza accounts for approximately €128 million in direct healthcare costs each season, with 80% of expenditures concentrated in individuals over 45 years of age. Vaccination remains the most effective intervention to prevent complications and reduce healthcare pressure. However, current coverage rates are consistently below international targets and continue to decline. In this context, there is an urgent need to strengthen vaccination uptake, especially among high-risk groups. Increasing vaccination uptake is essential to lessen the clinical, societal, and economic burden of influenza, since modest improvements in coverage have a significant impact on public health outcomes and economic resilience. In fact, previously published modeling analyses indicate that a 1% reduction in national vaccination coverage could result in over 6400 additional influenza cases and an additional economic burden of €1.54 million per season. Furthermore, increasing coverage to 75% in Spain could prevent approximately 180,300 additional cases—equivalent to 20% of the total—which would translate into potential savings of €43 million (€26 million in direct medical costs and €17 million in work absenteeism costs). This manuscript provides an overview of the influenza burden and vaccination landscape in Spain, focusing on clinical, societal, and economic implications of suboptimal coverage, as well as the current challenges and opportunities to improve uptake. Available evidence indicates that influenza vaccination reduces severe outcomes and healthcare burden, suggesting that mildly improving coverage in Spain could yield substantial health and economic benefits. Taken together, these findings support influenza vaccination as a public health priority and a relevant investment for health systems. Full article

We aimed to characterize age-stratified C-reactive protein (CRP) patterns across respiratory virus infections, assess age-related CRP shifts in virus-not-detected-by-PCR episodes, and evaluate the independent associations of age and virus type with CRP levels. We retrospectively analyzed 19,002 test-level episodes with paired respiratory PCR and serum CRP results from a single tertiary-care center between 2008 and 2024. Episodes were classified as virus-not-detected-by-PCR or virus-positive according to multiplex PCR results; the former was not considered a healthy control and may include off-panel infections, bacterial/mixed infections, false-negative results, or non-infectious inflammation. Descriptive analyses and multivariable linear regression of log-transformed CRP were used to assess adjusted associations. Median CRP increased with age in both virus-positive and virus-not-detected-by-PCR episodes, rising from 0.38 to 7.42 mg/dL across age groups in the latter. Age showed the strongest association with CRP. Adenovirus showed a positive adjusted association, whereas influenza A/B, respiratory syncytial virus A/B, and parainfluenza virus types 1 and 3 showed selective negative associations. Overall, CRP variation was more strongly associated with age-related clinical background than with virus type, although selective virus-associated differences were observed, supporting the interpretation of CRP as a non-specific, composite host-response indicator within broader clinical contexts. Full article

Background: Avian influenza is a critical zoonotic infection threatening both the poultry industry and global public health. While traditional intramuscular vaccines elicit systemic immunity, they often fail to provide robust local protection at mucosal surfaces. There is thus significant interest in the development of mucosal avian influenza vaccines administered via the intranasal route. However, in humans, this approach is significantly hampered by the availability of safe and effective adjuvants. Methods: This study investigated the immunogenicity of a modified recombinant influenza A/H5 hemagglutinin (rHA/H5-modif) formulated with Novochizol, a novel chitosan-derived delivery system, administered intranasally to laboratory animals. Results: Our results demonstrate that mucosal immunization with the rHA/H5-modif/Novochizol complex induces potent humoral (IgG and IgA) and cell-mediated immune responses. Crucially, the formulation provided 100% survival in mice following a lethal challenge with highly pathogenic avian influenza A/H5. Conclusions: These findings position the rHA/H5-modif/Novochizol complex as a promising candidate for next-generation mucosal vaccines, in particular against highly pathogenic avian influenza A/H5 subtype. Full article

Background/Objectives: The POLA index is a comprehensive tool for evaluating the nutrient-dense, immune-supportive, and anti-inflammatory properties of the diet, but its multi-component structure may limit routine use. We aimed to identify simple dietary markers associated with a lower follow-up incidence of COVID-19 or influenza, as well as the anti-inflammatory properties of the diet, and to compare a simplified screening tool with the full POLA index. Methods: This prospective observational study included 146 healthy adults aged 25–45 years from two Polish cohorts examined in 2020 and 2022 (cohort/year adjusted). Habitual diet was assessed using at least 5-day food records, and nutrient adequacy was expressed relative to Polish dietary reference values. Classification and regression tree analyses were used to identify the most informative dietary predictors of the reduction in risk of infection, and logistic regression models were used to evaluate associations after adjustment for sex, diet type, physical activity, marital status, year of cohort and waist-to-height ratio. Results: During follow-up, 39/146 participants (26.7%) reported COVID-19 or influenza. Interactive tree analysis identified dietary fiber in g per kg/m² of BMI ≥ 1, and magnesium adequacy as the key discriminators. In StrongPOLA, participants not meeting the cut-offs of ≥1 g fiber per kg/m² of BMI and ≥130% of the magnesium reference value had a higher incidence of COVID-19 or influenza than those meeting both of those cut-offs (34.9% vs. 2.7%); however, this estimate was large and imprecise, with a wide confidence interval (the adjusted OR = 14.9 (95% CI: 1.89–118.06)), and should, therefore, be interpreted cautiously. In RapidPOLA, the participants not meeting the cut-offs of ≥1 g fiber per kg/m² of BMI and ≥110% of the magnesium reference value (i.e., 352 mg/day for women and 462 mg/day for men) had a higher observed incidence of COVID-19 or influenza than those meeting both of those cut-offs (36.4% vs. 12.1%); the adjusted OR was 3.4 (95% CI: 1.18–8.75). RapidPOLA showed good agreement with the favorable result of the POLA classification (κ = 0.65). Conclusions: Dietary fiber in g per kg/m² of BMI and magnesium adequacy appear to be practical markers of a broader nutrient-dense, immune-supporting, and anti-inflammatory dietary pattern associated with a lower follow-up incidence of COVID-19 or influenza in young adults without comorbidities. RapidPOLA may be useful as a simple screening tool for a nutrient-dense, immune-supportive, and anti-inflammatory (NUTRIDIMAF) diet in young people without obesity and comorbidities, whereas StrongPOLA may serve as a stricter reference profile. The proposed cut-offs require external validation in independent and more diverse cohorts. Full article

During 2022–2024, a highly pathogenic avian influenza virus (HPAIV) H5N1 strain, designated A/Seagull/Hebei/qhd6/2024 (H5N1), was isolated from migratory birds in Beidaihe National Wetland Park, North China. Phylogenetic analyses revealed that its hemagglutinin (HA) gene belongs to the 2.3.4.4b clade, while the neuraminidase (NA) gene and internal genes clustered with strains originating from multiple continents, consistent with a transcontinental reassortment event. The virus also exhibited 90.1–98.1% nucleotide homology with human-derived H5N1 isolates. Molecular characterization identified key virulence-associated mutations, including the classic HPAIV HA cleavage site, HA-T160A (associated with enhanced human receptor-binding capacity), and NA-I117T (potentially linked to drug resistance). BALB/c mouse infection experiments confirmed systemic replication and high pathogenicity of strain qhd6, with a 50% lethal dose (LD50) of 0.95 log₁₀EID₅₀/mL. Antigenic analysis revealed good cross-reactivity with the widely used H5-Re14 vaccine strain. This study reports the identification, in Beidaihe National Wetland Park, of an HPAIV H5N1 strain whose genetic characteristics suggest intercontinental reassortment and indicate cross-species transmission risk. It clarifies the genetic characteristics and pathogenicity of this strain, providing an important theoretical and practical basis for precise surveillance, risk early warning, and comprehensive prevention and control of AIV at migratory bird stopover sites in North China. Full article

Background. Lower respiratory tract infections remain a major cause of morbidity and mortality in infants worldwide. Newborns possess an immature immune system but acquire passive immunity through maternal antibodies transferred via the placenta (IgG) and breast milk (IgA). Maternal vaccination may enhance this protection. This study aimed to quantify antibody levels against respiratory viruses in serum and breast milk from lactating women. Methods. Serum and breast milk samples were collected from 26 lactating mothers. Antibody levels were measured using an indirect enzyme-linked immunosorbent assay (ELISA) targeting seven viral antigens: influenza A (A/Thailand, A/California), influenza B (B/Phuket, B/Austria), SARS-CoV-2 (Spike and receptor-binding domain, RBD) and RSV F pre-fusion protein. Antibody isotypes IgG, IgA and IgM were analysed. Results. Virus-specific IgG and IgA antibodies were detected in all samples. Breast milk showed the highest levels of IgA, whereas serum contained higher IgG levels. A moderate positive correlation was observed between serum and milk IgG. No correlation was found between serum IgG and milk IgA, but both levels were elevated. Conclusions. Breast milk and serum contain relatively high levels of antibodies against the tested respiratory viruses. The elevated levels of serum IgG and milk IgA indicate a coordinated defence between systemic and mucosal immunity in response to infections. The levels and correlation of specific isotypes point to the source of the antibodies: milk IgG probably originates from the blood, whereas milk IgA is produced locally. Full article