Identification of Important N-Linked Glycosylation Sites in the Hemagglutinin Protein and Their Functional Impact on DC-SIGN Mediated Avian Influenza H5N1 Infection. 2021

Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

DC-SIGN, a C-type lectin mainly expressed in dendritic cells (DCs), has been reported to mediate several viral infections. We previously reported that DC-SIGN mediated H5N1 influenza A virus (AIVs) infection, however, the important DC-SIGN interaction with N-glycosylation sites remain unknown. This study aims to identify the optimal DC-SIGN interacting N-glycosylation sites in HA proteins of H5N1-AIVs. Results from NetNGlyc program analyzed the H5 hemagglutinin sequences of isolates during 2004-2020, revealing that seven and two conserved N-glycosylation sites were detected in HA1 and HA2 domain, respectively. A lentivirus pseudotyped A/Vietnam/1203/04 H5N1 envelope (H5N1-PVs) was generated which displayed an abundance of HA5 proteins on the virions via immuno-electron microscope observation. Further, H5N1-PVs or reverse-genetics (H5N1-RG) strains carrying a serial N-glycosylated mutation was generated by site-directed mutagenesis assay. Human recombinant DC-SIGN (rDC-SIGN) coated ELISA showed that H5N1-PVs bound to DC-SIGN, however, mutation on the N27Q, N39Q, and N181Q significantly reduced this binding (p < 0.05). Infectivity and capture assay demonstrated that N27Q and N39Q mutations significantly ameliorated DC-SIGN mediated H5N1 infection. Furthermore, combined mutations (N27Q&N39Q) significantly waned the interaction on either H5N1-PVs or -RG infection in cis and in trans (p < 0.01). This study concludes that N27 and N39 are two essential N-glycosylation contributing to DC-SIGN mediating H5N1 infection.

UI MeSH Term Description Entries
D007251 Influenza, Human An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia. Grippe,Human Flu,Human Influenza,Influenza in Humans,Influenza,Flu, Human,Human Influenzas,Influenza in Human,Influenzas,Influenzas, Human
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010802 Phylogeny The relationships of groups of organisms as reflected by their genetic makeup. Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015815 Cell Adhesion Molecules Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. Cell Adhesion Molecule,Intercellular Adhesion Molecule,Intercellular Adhesion Molecules,Leukocyte Adhesion Molecule,Leukocyte Adhesion Molecules,Saccharide-Mediated Cell Adhesion Molecules,Saccharide Mediated Cell Adhesion Molecules,Adhesion Molecule, Cell,Adhesion Molecule, Intercellular,Adhesion Molecule, Leukocyte,Adhesion Molecules, Cell,Adhesion Molecules, Intercellular,Adhesion Molecules, Leukocyte,Molecule, Cell Adhesion,Molecule, Intercellular Adhesion,Molecule, Leukocyte Adhesion,Molecules, Cell Adhesion,Molecules, Intercellular Adhesion,Molecules, Leukocyte Adhesion
D053122 Influenza A Virus, H3N2 Subtype A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 3 and neuraminidase 2. The H3N2 subtype was responsible for the Hong Kong flu pandemic of 1968. H3N2 Virus,H3N2v Viruses,Influenza A H3N2, Variant Virus,Influenza Virus, Canine, H3N2 Subtype,H3N2 Viruses,H3N2v Virus,Virus, H3N2,Virus, H3N2v,Viruses, H3N2,Viruses, H3N2v

Related Publications

Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
September 2008, Biochemical and biophysical research communications,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
February 2015, Archives of virology,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
May 2023, Glycobiology,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
August 2009, Bioinformation,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
January 2012, PloS one,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
April 2009, Virology journal,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
September 2012, Yonsei medical journal,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
January 2006, Methods in molecular biology (Clifton, N.J.),
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
July 2022, PNAS nexus,
Zih-Syuan Yang, and Szu-Wei Huang, and Wen-Hung Wang, and Chih-Yen Lin, and Chu-Feng Wang, and Aspiro Nayim Urbina, and Arunee Thitithanyanont, and Sung-Pin Tseng, and Po-Liang Lu, and Yen-Hsu Chen, and Sheng-Fan Wang
January 2018, Virology,
Copied contents to your clipboard!