Search Results (151)

H9N2 avian influenza virus (AIV) is widely prevalent in poultry in China. To understand the genetic characteristics and evolution of H9N2 AIVs in Guangxi, southern China, the complete genomes of H9N2 AIVs from 1999–2023 were systematically analysed. Maximum likelihood (ML) trees indicated that H9N2 AIV gene sublineage diversity contributed to genotype diversity, yielding 17 genotypes (G1–G17). Since 2010, genotype G14 (also known as genotype S or G57) has become predominant in poultry in Guangxi. Phylogenetic analysis in the HA has resulted in the distancing of recent Guangxi isolates from the vaccine strains. This study also revealed that the genotypes of H9N2 AIVs infecting swine, equines and canines in Guangxi were consistent with those found in avian species at the same time, highlighting the capacity of H9N2 AIVs to be transmitted across species. The antigenic residues in the HA head region and NA protein of the Guangxi isolates from 2020–2023 changed significantly compared to the vaccine strains, suggesting possible antigenic drift in these viruses. Amino acid analysis of the HA protein revealed that 84.9% (73/86) of H9N2 AIV isolates from Guangxi, including those from live poultry markets, preferentially bound to α-2,6 sialic acid receptors. Considerable attention should be given to cross-species transmission of H9N2 AIV in the region. On the basis of these findings, strengthening the monitoring of H9N2 AIV in poultry in Guangxi is essential. Full article

Siglec-10 is a cell-surface lectin that belongs to the sialic acid-binding immunoglobulin-like lectins (Siglecs) receptor involved in immune tolerance, but its role in reproduction remains unknown. Because immune regulation is essential for sperm survival and fertilization, Siglec-10 may represent an unexplored factor in camel fertility. Here, we investigated its expression and localization in the male reproductive tract and spermatozoa of dromedary camels during the rutting season. Testis, epididymis, and vas deferens were analyzed by immunohistochemistry and quantitative PCR, while spermatozoa from fresh ejaculates, frozen–thawed semen, and epididymal samples were examined using chromogenic and fluorescent immunostaining. Siglec-10 was strongly expressed in the testis and epididymis but absent in the vas deferens. In spermatozoa, the signal was localized mainly to the head and midpiece, with consistent patterns in fresh and frozen–thawed semen but absent in epididymal sperm. These findings provide the first descriptive evidence of Siglec-10 in camel reproductive tissues and ejaculated spermatozoa, suggesting a possible involvement in mechanisms that support sperm integrity under stress conditions; however, further studies are needed to clarify its functional role in semen preservation, and highlighting its relevance as a fertility biomarker in seasonal breeders. Full article

The H7N9 influenza viruses, which are capable of causing severe respiratory syndrome in humans, were first discovered to infect humans in 2013 and continue to pose a persistent public health threat. Quail has been proposed as a potential intermediate host that may facilitate the emergence of novel reassorted influenza A viruses with the capacity to infect humans across species barriers; however, information on the biological characterization of quail H7N9 remains limited. In this study, we isolated and identified an avian H7N9 influenza virus from quails, designated as A/quail/Hebei/CH06-07/2018 (H7N9) and abbreviated as CH06-07, in Hebei, China. Phylogenetic analyses revealed that both the HA gene and the NA gene of CH06-07 were clustered in the Eurasian lineage. Furthermore, CH06-07 exhibited binding affinity for both α2,3-linked and α2,6-linked sialic acid receptors and demonstrated high pathogenicity in both quails and mice. Notably, transmission studies revealed that CH06-07 not only exhibited efficient inter-quail transmission and inter-guinea pig transmission but also demonstrated effective cross-species transmission. Importantly, infected quails and guinea pigs generated significant quantities of viral aerosols (≥18,998 ± 1672 copies per liter of air at 3 days post-infection), and infectious viruses were successfully recovered from environmental aerosols. These findings highlight the necessity for continuous surveillance of the prevalence of quail-origin H7N9 influenza A viruses in poultry populations due to their potential threat to human health. Full article

The glycan profile of cells comprises a high variety of sugar moieties that are attached to proteins (glycoproteins) and lipids (glycolipids) via a process called ‘glycosylation’. Cancer cells commonly carry aberrant glycans, which may be of interest for cancer diagnosis, prognosis, as well as the development of novel therapeutic strategies. This review focuses on the differential glycosylation patterns on malignant B cells, including both B cell lymphoma and leukemia. Well-known aberrant glycan profiles on malignant B cells include acquired high mannose N-glycans in the B cell receptor (BCR) of follicular lymphoma (FL), and increased expression of the glycosphingolipid Gb3/CD77 on Burkitt’s lymphoma (BL). These structures can be exploited for therapy by using lectins that specifically recognize these patterns with intrinsic cytotoxic activity or in a drug-conjugate format. Furthermore, immunotherapy can be improved by modulating glycans, especially sialic acids. Targeting glycans for immunotherapy is also of interest for chimeric antigen receptor (CAR) T cell therapy, a relatively novel therapy that has been quite effective in various B cell malignancies. Thus, the glycan profile of malignant B cells harbors many opportunities for therapeutic targeting. It is anticipated that further in-depth glycan profiling will open up many more opportunities for the treatment of B cell malignancies. Full article

Background: Antibody-dependent cellular cytotoxicity (ADCC) is an immune response where antibodies bind to target cells and activate effector cells through Fcγ receptors, ultimately leading to the destruction of the target cells. Methods: This study examined the ADCC activities of charge variants of a therapeutic IgG₁, MAB1, using an internally developed reporter gene assay. In this assay, the proprietary target was expressed on DiFi cells, while FcγRIIIa was expressed on Jurkat effector cells. Results: The results revealed that different charge variants had varying levels of ADCC activity, with variants containing C-terminal lysine residues showing enhanced activity. The charge variants arose from modifications such as the presence of sialic acid at the glycan moiety, deamidation, and C-terminal lysine truncation, including K2 (two C-terminal lysine residues), K1 (one C-terminal lysine residue), and K0 (no C-terminal lysine residues) variants. Notably, the K1 and K2 variants demonstrated higher ADCC activity compared to the K0 and acidic variants. However, the observed increase was attributed not to the lysine residue itself, but rather to the MAN5 glycan associated with the lysine-containing variants. Conclusion: These findings challenge previous assumptions about the role of C-terminal lysine in ADCC, suggesting a shift in understanding the functional significance of charge variants and emphasizing the critical influence of glycan composition in therapeutic antibody efficacy. Full article

Enteroviruses (EVs), particularly those within the species Enterovirus A and B, represent a significant global public health burden, especially in infants and young children. While often causing self-limiting hand, foot, and mouth disease (HFMD), certain serotypes can lead to severe neurological and cardiopulmonary complications. This comprehensive review focuses on the major pathogenic serotypes, including enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6), coxsackievirus B3 (CV-B3), and enterovirus D68 (EV-D68). We began by reconstructing a phylogenetic tree based on VP1 protein sequences, elucidating the genetic relationships and evolutionary patterns among these serotypes, which underpin their diverse antigenicity and epidemiology. Building upon this genetic foundation, the review then provides a detailed synthesis of their distinct pathogenesis, highlighting the five-phase clinical progression from exanthematous phase to convalescence, and their unique tropisms for target organs such as the central nervous system and heart. Progressing to the molecular mechanisms, a critical component of this work is a systematic summary of the specific host receptors that mediate viral entry, including SCARB2 for EV-A71 and CV-A16, sialic acid and ICAM-5 for EV-D68, and CAR/CD55 for CV-B3, explaining the mechanistic basis for their tissue specificity and pathogenicity. Finally, to translate these insights into clinical applications, we critically evaluate the current landscape of vaccine development, noting the high efficacy (~90%) of inactivated EV-A71 vaccines in Asia and the significant global success of poliovirus vaccines, while also addressing the stark lack of cross-protective or licensed vaccines for other prevalent serotypes like CV-A16, CV-A6, and EV-D68. The review concludes that the high genetic diversity and serotype-specific immunity of enteroviruses pose a major challenge, necessitating a concerted shift towards the development of broad-spectrum vaccines and therapeutics informed by an integrated understanding of viral evolution, receptor usage, and pathogenesis. Full article

Background: Influenza, a primarily respiratory illness, frequently manifests with gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and abdominal pain. In this review, we analyze mechanisms describing GI infiltration and subsequent involvement of the GI system during influenza infection. Direct mechanisms involve the presence of viral particles in the GI tract and binding to sialic acid receptor, α2,3 and α2,6 linkages. The influenza virus may gain access to gut tissue via swallowing of respiratory secretions, hematogenous spread, or lymphocytic migration via the lung–gut axis. Indirect mechanisms involve immune system dysregulation via cytokine, interferon, and leukotriene flux, upregulation of consequential apoptotic pathways, or gut microbiome dysbiosis. Together, they promote secondary GI opportunistic infections. These findings improve our knowledge of GI infiltration during influenza infection which may aid in effective clinical diagnosis and treatment, ultimately improving patient outcomes. Full article

Background: Influenza A viruses (IAV) cause seasonal flu and occasional pandemics. In addition, the potential for the emergence of new strains presents unknown challenges for public health. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. Metal ions embedded into PPE have been demonstrated to inactivate respiratory viruses, but the underlying mechanism of inactivation and potential for resistance is presently not well understood. Methods: In this study, we used hemagglutination assays to quantify the effect of zinc ions on IAV sialic acid receptor binding. We varied the zinc concentration, incubation time, incubation temperature, and passaged IAV in the presence of zinc ions to investigate if resistance to zinc ions could evolve. Results: We found that zinc ions impact the ability of IAV particles to hemagglutinate and observed inhibition within 1 min of exposure. Maximum inhibition was achieved within 1 h and sustained for at least 24 h in a concentration-dependent manner. Inhibition was also temperature-dependent, and optimal above room temperature. Serial passaging of IAV in the presence of zinc ions did not result in resistance. Conclusions: e conclude that zinc ions prevent IAV hemagglutination in a concentration and temperature-dependent manner for at least 24 h. Overall, these findings are in line with previous observations indicating that zinc-embedded materials can inactivate the IAV hemagglutinin and SARS-CoV-2 spike proteins, and they support work toward developing robust, passive, self-cleaning antiviral barriers in PPE. Full article

Mature dendritic cells (DCs) are known to activate effector immune responses, whereas steady state immature DCs can induce tolerance. Several studies have targeted immature murine quiescent DCs in vivo with antigen, including donor alloantigens, for the induction of tolerance. Receptors expressed by specific DC subsets have been also targeted with antibodies linked with antigens to induce tolerance; for instance, in vivo targeting of the DCIR2⁺ DC subset with donor alloantigen resulted in long-term survival of heart and skin transplants. DCs also express sialic acid immunoglobulin-like lectin (Siglec) receptors, and these have been successfully targeted with myelin oligiodendrocyte glycoprotein (MOG) antigen to induce tolerance in experimental autoimmune encephalomyelitis (EAE). We investigated, in a mismatched model of skin transplant (B6K^d into B6 recipient mice), whether targeting a sialylated alloantigen K^d (Sia-K^d) to Siglecs on recipient DCs promoted transplant survival. The injection of α2,3 Sia-K^d into B6 recipient mice prior to B6K^d skin transplantation, by binding to Batf3 dependent DCs, resulted in prolonged skin graft survival and an increase in CD4⁺CD62L⁺Foxp3⁺ Tregs. Targeting Siglecs on DC subsets in vivo represents a novel way of improving transplant survival. Full article

Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation. The role of N-glycosylation was evaluated using Swainsonine (SW) and PNGase F. IαV glycoproteomic analysis was performed by mass spectrometry. Sialic acids and glycan structures in IαV/uPAR interaction were tested using neuraminidase A (NeuA) and lectin interference assays, respectively. Protein expression and their interaction were detected in GBM cells, but not in low-grade glioma cells, even in cells transfected to overexpress uPAR. SW, PNGase, and NeuA treatments significantly reduced IαV/uPAR interaction. Also, lectin interference assays indicated that β1-6 branched glycans play a crucial role in this interaction. Analysis of the IαV glycosylation profile revealed the presence of complex and hybrid N-glycans in GBM, while only oligomannose N-glycans were identified in low-grade glioma. N-glycosylation inhibition and sialic acid removal reduced AKT phosphorylation. Our findings demonstrate, for the first time, the interaction between IαV and uPAR in GBM cells, highlighting the essential role of N-glycosylation, particularly β1-6 branched glycans and sialic acids. Full article

The cross-species transmission of influenza viruses represents a critical link in the pandemic of zoonotic diseases. This mechanism involves multi-level interactions, including viral genetic adaptability, host–receptor compatibility, and ecological drivers. Recent studies have highlighted the essential role of mutations in hemagglutinin and neuraminidase in overcoming host barriers, while elucidating the differences in the distribution of host sialic acid receptors. Furthermore, the “mixer” function of intermediate hosts, such as pigs, plays a significant role in viral redistribution. Advances in high-throughput sequencing and structural biology technologies have gradually resolved key molecular markers and host restriction factors associated with these viruses. However, challenges remain in understanding the dynamic evolutionary patterns of virus–host interaction networks, developing real-time early warning capabilities for cross-species transmission, and formulating broad-spectrum prevention and control strategies. Moving forward, it is essential to integrate multidisciplinary approaches to establish a multi-level defense system, leveraging the ‘One Health’ monitoring network, artificial intelligence prediction models, and new vaccine research and development to address the ongoing threat of cross-species transmission of influenza viruses. This paper systematically reviews the research progress and discusses bottlenecks in this field, providing a theoretical foundation for optimizing future prevention and control strategies. Full article

Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes in OSCC have been related to grade, invasion, and metastasis. The presence of 9-O-acetylated sialic acid (Neu5,9Ac₂) in OSCC cells and its potential expression, modification, and role are unknown. This study aimed to analyze the expression of Neu5,9Ac₂ using the Macrobrachium rosenbergii lectin (MrL) that recognizes this sialic acid (Neu5Ac) residue and also compare its effect on the SCC-152 cell line (CRL-3240, ATCC) and immortalized keratinocytes (HaCaT) as a control. We observed by immunocytochemistry that SCC-152 cells expressed more Neu5,9Ac₂ compared to HaCaT cells; the specificity of MrL was confirmed after the sialidase treatment of cells in which the loss of lectin’s recognition of Neu5,9Ac₂ was observed. The electrophoretic profile was similar between both cell line types; however, the Western blot showed differences in the glycoprotein patterns recognized by lectin for each cell type. MrL increased the proliferation of SCC-152 cells, as well as the integrity and morphology of the colonies. Therefore, our results suggest that Neu5,9Ac₂ glycosylated receptors could be involved in the survival and proliferation of OSCC cells, which offers a promising avenue for developing diagnostic and prognostic tools (tumor markers) against oral squamous cell carcinoma in the future. Full article

Background/Objectives: The significance of cytokine signaling on cancer progression and metastasis has raised interest in cancer research over the last few decades. Here, we analyzed the effects of three cytokines that we previously reported are significantly upregulated rapidly after the surgical removal of primary breast, colorectal, and prostate cancer. We also investigated the regulation of their cognate receptors. Methods: All experiments were conducted using the PANC-1, SW620, and MCF-7 cell lines, treated with three different cytokines (TGF-β1, HGF, and IL-6). The effect of these cytokines on the expression of epithelial–mesenchymal transition (EMT) cell surface markers and neuraminidase-1 activity was measured via fluorescent microscopy and image analysis software. Results: The findings show that these cytokines increase the expression of mesenchymal markers while reducing epithelial markers, corresponding to the EMT process. A strong link between cytokine receptor signaling and the Neu-1-MMP-9-GPCR crosstalk was identified, suggesting that cytokine receptor binding leads to increased Neu-1 activity and subsequent signaling pathway activation. Oseltamivir phosphate (OP) prevented sialic acid hydrolysis by neuraminidase-1 (Neu-1), leading to the downregulation of these signaling cascades. Conclusions: In concert with the previous work revealing the role of Neu-1 in regulating other glycosylated receptors implicated in cancer cell proliferation and EMT, targeting Neu-1 may provide effective treatment against a variety of malignancies. Most significantly, the treatment of patients with specific inhibitors of Neu-1 soon after primary cancer surgery may improve our ability to cure early-stage cancer by inhibiting the EMT process and disrupting the ability of any residual cancer cell population to metastasize. Full article

This review summarizes recent findings on the diverse roles of bacterial sialidases in microbial biology. Bacterial sialidases, also known as neuraminidases, are exog α-lycosidases that cleave terminal sialic acid residues from a number of complex compounds designated as sialoglycoconjugates (glycoproteins, glycolipids and oligosaccharides). Metabolically, they are involved in sialic acid catabolism, providing energy, carbon and nitrogen sources. Catabolic degradation of sialic acids is a physiological feature that can be considered an important virulence factor in pathogenic microorganisms. Sialidases play a pivotal role in host–pathogen interactions and promotion of bacterial colonization. The activity of these enzymes enables bacterial adhesion, biofilm formation, tissue invasion, and also provides immune evasion by exposing cryptic receptors and modifying immune components. Many different perspectives are being developed for the potential application of sialidases. In the field of medicine, they are being explored as appropriate targets for antimicrobials, vaccines, diagnostic preparations and in tumor immunotherapy. In the field of enzymatic synthesis, they are used for the regioselective production of oligosaccharide analogs, enzymatic separation of isoenzymes and as a tool for structural analysis of sialylated glycans, among other applications. Full article

Rattus norvegicus (brown rat), a widely distributed rodent and common biomedical model, is a known reservoir for many zoonotic pathogens but has not been traditionally recognized as a host for influenza A virus (IAV). To evaluate their susceptibility, we intranasally inoculated Sprague-Dawley rats with various IAV subtypes, including H5Nx, H7N9, H9N2, H10N8 and the 2009 pandemic H1N1. All strains productively infected the rats, inducing seroconversion without overt clinical signs. While replication efficiency varied, all viruses caused significant lung injury with a preferential tropism for the upper respiratory tract. Investigation of receptor distribution revealed a predominance of α2,3-linked sialic acid (SA) in the nasal turbinates and trachea, whereas α2,6-linked SA was more abundant in the lungs. Notably, both receptor types coexisted throughout the respiratory tract, aligning with the observed tissue-specific replication patterns and broad viral infectivity. These findings demonstrate that rats are permissive hosts for multiple IAV subtypes, challenging their exclusion from IAV ecology. The asymptomatic yet pathogenic nature of infection, combined with the global synanthropy of rats, underscores their potential role as cryptic reservoirs in viral maintenance and transmission. This study highlights the need for expanded surveillance of rodents in influenza ecology to mitigate zoonotic risks. Full article