An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism.

Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus.

Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. IMPORTANCE Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses

Chewing lice of wild birds in Iran: new data and a checklist of avian louse species reported in Iran

Between September 2019 and December 2023, a total of 612 wild birds representing 16 orders, 33 families, 60 genera, and 78 species from nine provinces of Iran with different climates namely Hamedan (n = 54), Sistan-va-Baluchestan (n = 372), Kerman (n = 73), South Khorasan (n = 52), Mazandaran (n = 7), Chaharmahal-va-Bakhtiari (n = 2), Gilan (n = 2), Golestan (n = 18), North Khorasan (n = 9), and Razavi Khorasan (n = 23) were examined for chewing lice infestation. Naked eye examination revealed that 58 birds (9.5%) were infested with at least one chewing louse species. Collected lice specimens belonged to 28 species from the families Philopteridae, Menoponidae and Laemobothriidae including Strigiphilus strigis (n = 55, 15.6%), Falcolipeurus quadripustulatus (n = 41, 11.6%), Craspedorrhynchus platystomus (n = 40, 11.3%), Colpocephalum turbinatum (n = 36, 10.2%), Laemobothrion maximum (n = 25, 7.1%), Nosopon lucidum (n = 20, 5.6%), Degeeriella fulva (n = 18, 5.1%), Colpocephalum eucarenum (n = 16, 4.5%), Laemobothrion vulturis (n = 15, 4.2%), Anaticola crassicornis (n = 13, 3.7%), Craspedorrhynchus aquilinus (n = 9, 2.5%), Degeeriella fusca (n = 7, 2.0%), Aegypoecus trigonoceps (n = 7, 2.0%), Quadraceps obscurus (n = 6, 1.7%), Colpocephalum impressum (n = 6, 1.7%), Trinoton querquedulae (n = 6, 1.7%), Colpocephalum heterosoma (n = 5, 1.4%), Colpocephalum nanum (n = 5, 1.4%), Lunaceps holophaeus (n = 4, 1.1%), Quadraceps spp. (n = 4, 1.1%), Actornithophilus uniseriatus (n = 2, 0.6%), Nosopon chanabense (n = 2, 0.6%), Actornithophilus cornutus (n = 1, 0.3%), Cuclotogaster heterographus (n = 1, 0.3%), Falcolipeurus suturalis (n = 1, 0.3%), Laemobothrion atrum (n = 1, 0.3%), Colpocephalum gypsi (n = 1, 0.3%), and Rallicola cuspidatus (n = 1, 0.3%). All of these species except six, i.e., Trinoton spp., C. aquilinus, L. vulturis, L. maximum, C. impressum, C. turbinatum, and C. heterographus are recorded for the first time from Iran. This study is the largest epidemiological study to date performed in the country. Data reported herein contribute to our knowledge about diversity of avian chewing lice from wild birds in Iran. In this paper, an updated checklist of louse species reported from Iran according to their avian hosts is presented

Bacteria of Phlebotominae Sand Flies Collected in Western Iran

Microorganisms particularly bacteria presenting in insects such as Phlebotominae may play an important role in the epidemiology of human infectious disease. Nowadays, because of vector implications, the routine methods of controlling and spraying have no more beneficial effects on vectors and reservoirs. Little knows about the prevalence and diversity of sand fly bacteria. The main objective of this study was to determine the presence of bacteria of phlebotominae sand flies collected in Hamadan, west of Iran. This information is important in order to development of vector control strategies. The microbial flora of Phlebotomus papatasi and P. sergenti the main vector of Cutaneous Leishmaniasis in the old world, were investigated. We characterized 8 bacteria, including 5 Gram-negative bacteria: Acinetobacter lwoffii, Pseudomonas aeruginosa, Enterobacter cloacae, Edvardsiela sp. and Proteus mirabilis and Gram-positive bacteria: Bacillus subtilis, Staphylococcus saprophyticus and Micrococcus luteus. Our study provides some data on the microbiota diversity of field-collected sand flies for the first time in Hamadan. Our results indicate that there is a range of variation of aerobic bacteria inhabiting sand fly, which possibly reflect the ecological condition of the habitat where the fly breeds. Microbiota is increasingly regarded as an important factor for modulating vector competence in insect vectors. So, mirobiota can be effects on the biology of phlebotominae and their roles in the sandfly-Leishmania interaction. Further experiments are required to clearly delineate the vectorial role of sand flies. Because it is probable that in the future, factors such as environmental changes, migration and urbanization can ease the transmission of leishmaniasis in this area

Ionic liquid 1-butyl-3-methylimidazolium bromide ([bmim]Br): a green and neutral reaction media for the efficient, catalyst-free synthesis of quinoxaline derivatives

Quinoxaline derivatives were produced in excellent yields and short reaction times via the condensation of 1,2-diamines with 1,2-diketones in the neutral ionic liquid 1-butyl-3-methylimidazolium bromide ([bmim]Br) under catalyst-free and microwave irradiation conditions

Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1.

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection

Polyclonal human antibodies against glycans bearing red meat-derived non-human sialic acid N-glycolylneuraminic acid are stable, reproducible, complex and vary between individuals: Total antibody levels are associated with colorectal cancer risk.

BACKGROUND: N-glycolylneuraminic acid (Neu5Gc) is a non-human red-meat-derived sialic acid immunogenic to humans. Neu5Gc can be metabolically incorporated into glycan chains on human endothelial and epithelial surfaces. This represents the first example of a "xeno-autoantigen", against which circulating human "xeno-autoantibodies" can react. The resulting inflammation ("xenosialitis") has been demonstrated in human-like Neu5Gc-deficient mice and contributed to carcinoma progression via antibody-mediated inflammation. Anti-Neu5Gc antibodies have potential as biomarkers for diseases associated with red meat consumption such as carcinomas, atherosclerosis, and type 2 diabetes. METHODS: ELISA assays measured antibodies against Neu5Gc or Neu5Gc-glycans in plasma or serum samples from the Nurses' Health Studies, the Health Professionals Follow-up Study, and the European Prospective Investigation into Cancer and Nutrition, including inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over 1-3 years in archived samples. We also assessed associations between antibody levels and coronary artery disease risk (CAD) or red meat intake. A glycan microarray was used to detected antibodies against multiple Neu5Gc-glycan epitopes. A nested case-control study design assessed the association between total anti-Neu5Gc antibodies detected in the glycan array assay and the risk of colorectal cancer (CRC). RESULTS: ELISA assays showed a wide range of anti-Neu5Gc responses and good inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over time, but these antibody levels did not correlate with CAD risk or red meat intake. Antibodies against Neu5Gc alone or against individual Neu5Gc-bearing epitopes were also not associated with colorectal cancer (CRC) risk. However, a sialoglycan microarray study demonstrated positive association with CRC risk when the total antibody responses against all Neu5Gc-glycans were combined. Individuals in the top quartile of total anti-Neu5Gc IgG antibody concentrations had nearly three times the risk compared to those in the bottom quartile (Multivariate Odds Ratio comparing top to bottom quartile: 2.98, 95% CI: 0.80, 11.1; P for trend = 0.02). CONCLUSIONS: Further work harnessing the utility of these anti-Neu5Gc antibodies as biomarkers in red meat-associated diseases must consider diversity in individual antibody profiles against different Neu5Gc-bearing glycans. Traditional ELISA assays for antibodies directed against Neu5Gc alone, or against specific Neu5Gc-glycans may not be adequate to define risk associations. Our finding of a positive association of total anti-Neu5Gc antibodies with CRC risk also warrants confirmation in larger prospective studies

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

Ruminococcus gnavus is a human gut symbiont which ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid binding carbohydrate binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis, and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 b-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut