Fig 4
Binding of anti-sialyl-Lewis x (SLX) and Vim-2 (VIM) monoclonal antibodies to upper phase gangliosides (after Folch's partition) of human leukocytes separated on silica gel TLC plates. Anis, gangliosides stained with anisaldehyde; Virus, gangliosides overlaid with human influenza virus HRP conjugate. The plates were developed in (A) chloroform/methanol/0.25% KCl, 50:55:13, and (B) chloroform/methanol/0.25% KCl, 50:40:10.
Source publication
A human strain of influenza virus (A, H1N1) was shown to bind in an unexpected way to leukocyte and other gangliosides when compared with avian virus (A, H4N6) as assayed on TLC plates. The human strain bound only to species with about 10 or more sugars, while the avian strain bound to a wide range of gangliosides including the 5-sugar gangliosides...
Contexts in source publication
Context 1
... test if the binding of the human virus was to the mono- fucosylated sialyl-Lewis x or VIM-2-active saccharides as reported earlier (Suzuki, 1994;Müthing, 1996), we used overlay of TLC plates with antibodies which react with these structures ( Figure 4). The polar solvent (A) allowed clear sepa- ration of VIM-2-and virus-positive fractions ( Figure 4A, lanes VIM and Virus), at least within the less complex region. ...
Context 2
... test if the binding of the human virus was to the mono- fucosylated sialyl-Lewis x or VIM-2-active saccharides as reported earlier (Suzuki, 1994;Müthing, 1996), we used overlay of TLC plates with antibodies which react with these structures ( Figure 4). The polar solvent (A) allowed clear sepa- ration of VIM-2-and virus-positive fractions ( Figure 4A, lanes VIM and Virus), at least within the less complex region. There was an overlapping of anti-sialyl-Lewis x and human virus bindings ( Figure 4A and 4B, lanes SLX and Virus), but the patterns were not identical, and there was no recognition by the virus of less complex sialyl-Lewis x-positive molecules. ...
Context 3
... polar solvent (A) allowed clear sepa- ration of VIM-2-and virus-positive fractions ( Figure 4A, lanes VIM and Virus), at least within the less complex region. There was an overlapping of anti-sialyl-Lewis x and human virus bindings ( Figure 4A and 4B, lanes SLX and Virus), but the patterns were not identical, and there was no recognition by the virus of less complex sialyl-Lewis x-positive molecules. Figure 5 shows binding of MAA and SNA (lectins specific for α3-and α6-linked NeuAc, respectively) to leukocyte gangliosides in comparison with binding by human influenza virus. ...
Context 4
... could not identify the binding structure because of the small amount of the material. However, we have excluded sialyl-Lewis x and VIM-2-active saccharides (Table I, Figure 4) as the binding sequences. We have also shown using SNA lectin that the binding was to some minor NeuAcα6-containing species ( Figure 5). ...
Context 5
... results therefore do not support earlier suggestions on a preferential binding of human influenza A viruses to sialyl-Lewis x (Suzuki, 1994) or VIM-2-active structures (Suzuki, 1994;Müthing, 1996 Souza, 1989;Matrosovich et al., 1997), and this may explain strong interaction of PR/8/34 and X-31 with sialyl-Lewis x and VIM-2 structures and no binding to these structures in our tests. There was an overlapping binding by anti-sialyl-Lewis x antibody and the human virus in our studies (Figure 4). However, the overall patterns were not identical and there was no interaction of the virus with less complex sialyl-Lewis x gangliosides reported to be present in human leukocytes (Müthing et al., 1996). ...
Context 6
... the overall patterns were not identical and there was no interaction of the virus with less complex sialyl-Lewis x gangliosides reported to be present in human leukocytes (Müthing et al., 1996). We have detected by FAB MS in fractions 1 through 3 ( Figure 6) increasing amounts of 8s gangliosides with a potential sialyl-Lewis Of importance is a binding in this region of anti-sialyl-Lewis x antibody, but not of either VIM-2 antibody or virus (Figure 4). Structural microheterogeneity associated with ceramide parts and NeuAc α3/α6 substitutions may explain the overlapping migration of different gangliosides and the complex multi- band patterns in lanes SLX of Figure 4. ...
Context 7
... have detected by FAB MS in fractions 1 through 3 ( Figure 6) increasing amounts of 8s gangliosides with a potential sialyl-Lewis Of importance is a binding in this region of anti-sialyl-Lewis x antibody, but not of either VIM-2 antibody or virus (Figure 4). Structural microheterogeneity associated with ceramide parts and NeuAc α3/α6 substitutions may explain the overlapping migration of different gangliosides and the complex multi- band patterns in lanes SLX of Figure 4. The cross-binding to other fucosylated structures (Stroud et al., 1995) of the lower TLC regions, may also contribute to these complex patterns. ...
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Background:
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Citations
... The receptor-binding site of H7tu has a 100% identity with our H7N7 HPAIV used for in vitro and in vivo characterization. Since the complex glycan structure can influence receptor binding (14,(22)(23)(24)(25), we here focused on biologically relevant complex N-glycans presenting α2,3-linked NeuAc, α2,3-linked NeuGc, α2,6-linked NeuAc, and sLe X epitopes (Fig. 3A). These glycans were printed on glass slides, and after incubation of the slides with the viruses, HAs, and fluorescent secondary antibodies, the glycan-HA binding was evaluated. ...
... Previously, we only detected binding to glycans terminating in α2,3-linked NeuAc (33); here, we observed a strong preference for tri-antennary N-glycans presenting at least one sLe X epitope (glycans 25-28, Fig. 3B), which is near identical to the virus. Both glycans solely presenting sLe X epitopes (27,28) and glycans presenting an sLe X on one arm and α2,3-linked NeuAc on the other two arms (25,26) were bound. For the latter, it cannot be distinguished whether binding is caused by the sLe X or the α2,3-linked NeuAc. ...
Influenza A viruses (IAVs) can overcome species barriers by adaptation of the receptor-binding site of the hemagglutinin (HA). To initiate infection, HAs bind to glycan receptors with terminal sialic acids, which are either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc); the latter is mainly found in horses and pigs but not in birds and humans. We investigated the influence of previously identified equine NeuGc-adapting mutations (S128T, I130V, A135E, T189A, and K193R) in avian H7 IAVs in vitro and in vivo. We observed that these mutations negatively affected viral replication in chicken cells but not in duck cells and positively affected replication in horse cells. In vivo, the mutations reduced virus virulence and mortality in chickens. Ducks excreted high viral loads longer than chickens, although they appeared clinically healthy. To elucidate why these viruses infected chickens and ducks despite the absence of NeuGc, we re-evaluated the receptor binding of H7 HAs using glycan microarray and flow cytometry studies. This re-evaluation demonstrated that mutated avian H7 HAs also bound to α2,3-linked NeuAc and sialyl-LewisX, which have an additional fucose moiety in their terminal epitope, explaining why infection of ducks and chickens was possible. Interestingly, the α2,3-linked NeuAc and sialyl-LewisX epitopes were only bound when presented on tri-antennary N-glycans, emphasizing the importance of investigating the fine receptor specificities of IAVs. In conclusion, the binding of NeuGc-adapted H7 IAV to tri-antennary N-glycans enables viral replication and shedding by chickens and ducks, potentially facilitating interspecies transmission of equine-adapted H7 IAVs.
IMPORTANCE
Influenza A viruses (IAVs) cause millions of deaths and illnesses in birds and mammals each year. The viral surface protein hemagglutinin initiates infection by binding to host cell terminal sialic acids. Hemagglutinin adaptations affect the binding affinity to these sialic acids and the potential host species targeted. While avian and human IAVs tend to bind to N-acetylneuraminic acid (sialic acid), equine H7 viruses prefer binding to N-glycolylneuraminic acid (NeuGc). To better understand the function of NeuGc-specific adaptations in hemagglutinin and to elucidate interspecies transmission potential NeuGc-adapted viruses, we evaluated the effects of NeuGc-specific mutations in avian H7 viruses in chickens and ducks, important economic hosts and reservoir birds, respectively. We also examined the impact on viral replication and found a binding affinity to tri-antennary N-glycans containing different terminal epitopes. These findings are significant as they contribute to the understanding of the role of receptor binding in avian influenza infection.
... Miller-Podraza et al. [159,183] investigated how avian and human influenza viruses bind to gangliosides obtained from diverse human tissues and cells, with a particular focus on leukocytes. MALDI-TOF MS was performed on a TofSpec-E (Micromass, Manchester, UK) using ATT as a matrix, to elucidate the structural characteristics of gangliosides and identify the specific ganglioside species responsible for virus binding. ...
... In contrast, the avian influenza virus displayed broader binding capabilities, interacting with various gangliosides across all tested tissues. It showed an affinity for species which are NeuAcα 3 Gal-terminated, as evidenced by its binding to NeuAcα 3 -paragloboside (S-3-PG) and GD1a and GT1b gangliosides [183]. ...
Glycosphingolipids (GSLs) are a glycolipid subtype which plays vital roles in numerous biological processes, cell–cell interactions, as well as oncogenesis and ontogenesis. They are ubiquitous molecules found mostly in cell membranes. Abnormal expression of GSLs as well as altered molecular structure have been linked with progression of cancer and metastasis and are involved in the pathophysiology of neurodegenerative, autoimmune, and infectious diseases as well as inherited enzyme defects—glycosphingolipidoses. Matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) plays a leading role in analyzing and characterizing different GSLs, and thus can help to distinguish altered GSL patterns. This review offers insights into the benefits and limitations when using MALDI MS in this field of lipidomic research, with an emphasis on which are the optimal matrices in analyzing GSLs from different tissues (normal and pathological) as well as highlighting GSLs’ particular profiles in various cell cultures, and normal and pathological human tissues obtained by MALDI non-imaging MS (non-IMS). These findings can have implications in further understanding the role of altered GSL expression in various pathological conditions and could be a target for future therapies.
... Lastly, gangliosides act as receptors for a wide variety of pathogens such as viruses (influenza, simian, polyomavirus) (Miller-Podraza et al., 2000;Campanero-Rhodes et al., 2007;You et al., 2015), bacteria (M. ...
Botulinum toxins (BoNTs) comprise a family of extremely potent neurotoxins, which have been harnessed as muscle relaxants for the treatment of a wide variety of debilitating diseases, particularly for the treatment of movement disorders. BoNT entry into neurons leads to destructive cleavage of cellular proteins critical to vesicle fusion and neurotransmitter release at the neuromuscular junction. A dual receptor model has been proposed for BoNT binding to target neurons, comprising a low affinity ganglioside interaction followed by a higher affinity interaction with a protein receptor. A deeper understanding of the molecular nature of these interactions will facilitate the generation of modified BoNT proteins with novel characteristics and significant therapeutic potential. This project was aimed principally at molecular characterisation of the interaction of BoNT/A with gangliosides, using a combination of computational, biochemical, and biophysical methods. Specific achievements included: 1) The development and optimisation of two biophysical protocols for measuring Botulinum neurotoxin binding to gangliosides. 2) The preparation of a well curated carbohydrate database that contained all known structures of protein-carbohydrate. 3) The generation of a comprehensive and meaningful benchmark for algorithms that are designed to predict affinity values for protein-small molecule interactions. 4) The training of a state-of-the-art machine learning algorithm that can predict affinity values for protein-small molecule interactions. 5) The use of computational and biophysical approaches to explore the specificity and selectivity of ganglioside binding pockets. The objective was to make contributions to the development of an engineered BoNT with novel binding properties and therapeutic potential. In addition, a set of novel tools and methodologies that can be applied across most types of structural data was developed. In addition to the main project this thesis describes a series of collaborative efforts, not directly related to BoNTs, that were undertaken during my PhD. This section focuses mainly on projects related to the COVID-19 pandemic, which heavily disrupted ordinary research work, as well as a parallel project modelling the proteome of Mycobacterium abscessus.
... On the other hand, H1 strongly bound to IV 6 Neu5Ac-nLc4-PE with tetrasaccharide core as well as SNL (whereby the MAL reference was again negative), whereas H7 showed only low binding intensity. However, the utilized short linear receptor portions, i.e. a sialylated di-and tetrasaccharide, are more likely inadequate for a detailed analysis of the H1 and H7 fine specificities, because human virus hemagglutinins bind vastly preferentially to extended glycan receptors with a number of Galβ1-4GlcNAc-repeats beneath the terminal α2-6-sialoside moiety (Miller-Podraza et al. 2000;Matrosovich et al. 2009;Peng et al. 2017). Importantly, it should be mentioned as a cautionary note that a protein label such as polyhistidine tag or biotin can influence specificity of interaction analysis through possible charge effect or spatial hindrance. ...
Real-time interaction analysis of H1 hemagglutinin from influenza A H1N1 (A/New York/18/2009) and H7 hemagglutinin from influenza A H7N7 (A/Netherlands/219/03) with sialylated neoglycolipids (neoGLs) was performed using the surface acoustic wave (SAW) technology. The produced neoGLs carried phosphatidylethanolamine (PE) as lipid anchor and terminally sialylated lactose (Lc2, Galβ1-4Glc) or neolactotetraose (nLc4, Galβ1-4GlcNAcβ1-3Galβ1-4Glc) harbouring an N-acetylneuraminic acid (Neu5Ac). Using α2-6-sialylated neoGLs, H1 and H7 exhibited marginal attachment towards II6Neu5Ac-Lc2-PE, whereas Sambucus nigra lectin (SNL) exhibited strong binding and Maackia amurensis lectin (MAL) was negative in accordance with their known binding preference towards a distal Neu5Acα2-6Gal- and Neu5Acα2-3Gal-residue, respectively. H1 revealed significant binding towards IV6Neu5Ac-nLc4-PE when compared to weak interaction of H7, while SNL showed strong and MAL no attachment corresponding to their interaction specificities. Additional controls of MAL and SNL with α2-3-sialylated II3Neu5Ac-Lc2-PE and IV3Neu5Ac-nLc4-PE underscored the reliability of the SAW technology. Pre-exposure of model membranes spiked with α2-6-sialylated neoGLs to Vibrio cholerae neuraminidase substantially reduced the binding of the hemagglutinins and the SNL reference. Collectively, the SAW technology is capable of accurate measuring binding features of hemagglutinins towards neoGL-spiked lipid bilayers, which can be easily loaded to the functionalized biosensor gold surface thereby simulating biological membranes and suggesting promising clinical application for influenza virus research.
... Influenza virus initially colonizes nonciliated epithelial cells in the tracheobronchial tree via a sialic acid-specific viral hemagglutinin. Studies of animal and human strains show that virus binding is dependent on the neuraminic acid type (NeuAc or NeuGc) and the glycosidic linkage (␣2-3 or ␣2-6) and is influenced by fucosylation and the length of the polylactosamine scaffold (300)(301)(302)(303). Human strains typically prefer terminal NeuAc␣2-6Gal epitopes, which are richly expressed along the upper respiratory tract (304,305). ...
Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
... Similarly, such selectivity toward different gangliosides might also be implicated in membrane dynamics and trafficking (in addition to signaling), due to the synergistic interplay of glycoproteins and GSLs in recognition, binding and stabilization of receptor sites (35). For example, EGFR signaling is a regulator of influenza virus entry into host cells (36) and, interestingly, influenza virus exhibits similar specificities toward gangliosides with internally attached sialic acids such as GD1b and GT1b (37)(38)(39). ...
... Thus, in this particular case, gangliosides with two internal sialic acids are molecular 'markers' that correlate with endosomal sorting and uptake of toxins into the host cytoplasm. Similarly, influenza virus entering host cells from LE shows a higher specificity toward gangliosides GD1b and GT1b (both gangliosides with two internal sialic acids) while binding to other gangliosides such as GD1a (which carries only one internal sialic acid, Figure 1B) is rather unspecific (37)(38)(39). Furthermore, αgalactosyl derivatives of the ganglioside GD1b have also been implicated in receptor-mediated endocytosis of the mast cell receptor FcεRI and its trafficking to LE and lysosomes (98,99). ...
Gangliosides, glycosphingolipids containing sialic acid moieties, are well known mediators of transmembrane signalling and endocytosis at the plasma membrane. However, little is known about their precise regulatory role at the cell periphery for intracellular sorting of extracellular cargo. Here we inspected published scientific literature for two types of cargoes, namely bacterial toxins and viruses, regarding their usage of gangliosides. We derived a rather simple yet surprisingly consistent framework to classify 20 viruses from 12 different families and 5 type AB bacterial toxins into two broad categories. We propose that gangliosides with terminally attached sialic acids classify cargo for uptake and trafficking early in the endocytic pathway while gangliosides with internally attached sialic acids associate with uptake and trafficking of cargo late in the endocytic system. Our study provides a testable hypothesis for future investigations into a wide range of trafficking events. It could be utilized as a framework for other intracellular pathogens where lipids are known to be involved in recognition and trafficking. For instance, predictions can be put forward and evaluated based on ganglioside binding patterns and intracellular trafficking routes. Finally, incorporation of our classifier into large scale systems-biology studies could help reveal related molecular determinants in subcellular sorting.
... Although they are minor cell membrane compounds, microdomain-associated GSLs mediate profound physiological processes (e.g., cell adhesion, motility, and cell growth [21][22][23][24][25] ) and are involved in transmembrane signaling despite restriction to the outer bilayer leafl et (25)(26)(27)(28). Furthermore, cell surface-exposed oligosaccharides protruding into the extracellular environment make GSLs excellent recognition structures for numerous pathogens, such as infl uenza viruses ( 29,30 ) and bacteria ( 31,32 ), and for bacterial toxins including Shiga toxins (Stxs) ( 33,34 ). ...
Glycosphingolipids (GSLs) of the globo-series constitute specific receptors for Shiga toxins (Stxs) released by certain types of pathogenic Escherichia coli strains. Stx-loaded leukocytes may act as transporter cells in the blood and transfer the toxin to endothelial target cells. Therefore, we performed a thorough investigation on the expression of globo-series GSLs in serum-free cultivated Raji and Jurkat cells, representing B- and T-lymphocyte descendants, respectively, as well as THP-1 and HL-60 cells of the monocyte and granulocyte lineage, respectively. The presence of Stx-receptors in GSL preparations of Raji and THP-1 cells, but absence in Jurkat and HL-60 cells, revealed high compliance of solid phase immunodetection assays with the expression profiles of receptor-related glycosyltransferases, performed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and Stx2-caused cellular damage. Canonical microdomain association of Stx GSL receptors, sphingomyelin, and cholesterol in membranes of Raji and THP-1 cells was assessed by comparative analysis of detergent-resistant membrane (DRM) and nonDRM fractions obtained by density gradient centrifugation and showed high correlation based on nonparametric statistical analysis. Our comprehensive study on the expression of Stx-receptors and their subcellular distribution provides the basis for exploring the functional role of lipid raft-associated Stx-receptors in cells of leukocyte origin.
... However, the lack of definitive structural data at that time hampered rationalization of high virusbinding activity of polyglycosylceramides. In a follow-up study using a ganglioside preparation from human leukocytes, the same research group could show an unexpected binding of a human H1N1 influenza A strain (human X-113 reassortant of A/Texas/36/91, H1N1, and avian virus A/duck/ Czechoslovakia/56, H4N6) to extended (but not short) ganglioside species with about 10 or more sugars (Miller-Podraza et al. 2000). The virus-binding pattern did not follow binding by VIM-2 mAb and was not identical with binding by anti-sLe x antibody. ...
... Despite the fact that numerous influenza A viruses have been shown to bind to TLC-separated gangliosides as well as to gangliosides inserted into model membranes or employed in microwell adsorption assays (Suzuki 1994;Matrosovich et al. 1996Matrosovich et al. , 1997Miller-Podraza et al. 2000;Hidari et al. 2007), their involvement in the biological process of virus attachment to the cell surface and subsequent endocytotic uptake remains unclear. A large number of influenza A viruses bind to gangliosides of the neolacto-series and/or complex type N-glycans of glycoproteins decorated with the analogous α2-3and/or α2-6-sialylated Galβ1-4GlcNAc-disaccharide chains. ...
Among influenza A viruses, subtype H3N2 is the major cause of human influenza morbidity and is associated with seasonal epidemics causing annually half million deaths worldwide. Influenza A virus infection is initiated via hemagglutinin that binds to terminally sialylated glycoconjugates exposed on the surface of target cells. Gangliosides from human granulocytes were probed using thin-layer chromatography overlay assays for their binding potential to H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. Highly polar gangliosides with poly-N-acetyllactosaminyl chains showing low chromatographic mobility exhibited strong virus adhesion which was entirely abolished by sialidase treatment. Auxiliary overlay assays using anti-sialyl Lewis(x) (sLe(x)) monoclonal antibodies showed identical binding patterns compared with those performed with the viruses. A comprehensive structural analysis of fractionated gangliosides by electrospray ionization quadrupole time-of-flight mass spectrometry revealed sLe(x) gangliosides with terminal Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc epitope and extended neolacto (nLc)-series core structures as the preferential virus binding gangliosides. More precisely, sLe(x) gangliosides with nLc8, nLc10 and nLc12Cer cores, carrying sphingosine (d18:1) and a fatty acid with variable chain length (mostly C24:0, C24:1 or C16:0) in the ceramide moiety and one or two additional internal fucose residues in the oligosaccharide portion, were identified as the preferred receptors recognized by H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. This study describes glycan-binding requirements of hemagglutinin beyond binding to glycans with a specific sialic acid linkage of as yet undefined neutrophil receptors acting as ligands for H3N2 viruses. In addition, our results pose new questions on the biological and clinical relevance of this unexpected specificity of a subtype of influenza A viruses.
... Since fine receptor specificity existed in H5N1 viruses [9][10] , the glycan array including sulfated-, fucosylated-, linear sialosides, di-sialosides or direct binding assay with synthetic polyacrylamide(PAA)-based sialylglycopolymers was also recommended for the receptorspecificity surveillance on H5N1 viruses. Furthermore, the long-branched α2, 6 sialylated glycans were currently identified to predominate on the upper respiratory epithelial in humans and the recognition of this topology, 6'SLN-LN is the key determinant for the human-adaptation of influenza A virus [11] . ...
... With the adaptation from wild aquatic birds to domestic poultry or even in human host environment, influenza virus may possess broader carbohydratebinding spectrum or topology conformation [11,14] . We demonstrated differential α2, 6-binding property of two human H5N1 viruses, A/GD/1/06 and A/GX/1/08. ...
... We demonstrated differential α2, 6-binding property of two human H5N1 viruses, A/GD/1/06 and A/GX/1/08. Though minor effect of short-α2, 6-binding was detected in viruses A/GX/1/08 at a low virus titer, both were of high affinity to long-α2, 6 glycans, even at the low titer which are rich on apical side of human upper respiratory epithelia [11] . Notably, no evident binding preference switching was detected in the viruses isolated from the sporadic human infection cases in early 2009 in China (Table 1). ...
Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-linked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China.
The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell (CRBC) agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers.
Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains: A/Guangdong/1/06 (A/GD/1/06) and A/Guangxi/1/08 (A/GX/1/08). Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses.
The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.
... The initial step of viral attachment to the susceptible cell is crucial in the process of establishing an infection. The sialic acid motif, which is widely presented on acidic GSLs, is perhaps the most broadly recognised adhesion component utilised by viruses, from small non-enveloped DNA polyomaviruses to larger enveloped RNA influenza viruses (Gilbert & Benjamin, 2004, Miller-Podraza et al., 2000, Tsai et al., 2003). The GSL neolactotetraosylceramide (nLc 4 Cer) is a key receptor for the enveloped Dengue virus, an infectious agent transmitted by mosquitoes (Aoki et al., 2006). ...
