Giuseppe
Emeritus
NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus. (J Virol., abstract, edited)
7. J Virol. 2010 Feb 10. [Epub ahead of print]
NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus.
Mendelson M, Tekoah Y, Zilka A, Gershoni-Yahalom O, Gazit R, Achdut H, Bovin NV, Segman-Meningher T, Mandelboim M, Mandelboim O, David A, Porgador A. - The Shraga Segal Department of Microbiology and Immunology and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, Israel; Center for Glycobiology, Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow GSP-7, 117997, Russia; Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer Israel; The Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Natural killer (NK) cells serve as a crucial first line defense against tumors and virus-infected cells. We previously showed that lysis of influenza virus (IV)-infected cells is mediated by the interaction between the NK receptor, NKp46, and the IV-hemagglutinin type 1 expressed by the infected cells. This interaction requires the presence of sialyl groups on the NKp46-T225-O-glycoforms. In the current study we analyzed the O-glycan sequences imperative for the interaction between recombinant NKp46 (rNKp46) and IV-H1N1 strains. We first showed that rNKp46 binding to IV-H1N1 is not mediated by a glycoform unique to the T225 site. We then characterized the O-glycan sequences that mediate the interaction of rNKp46 and IV-H1N1; we employed rNKp46s with dissimilar glycosylation pattern and IV-H1N1 strains with different preference to sialic acid alpha2,3 and alpha2,6 linkages. Branched alpha2,3 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,4-GlcNAcbeta1,6[Neu5NAcalpha2,3-Galbeta1,3]GalNAc, competently mediate the interaction of rNKp46 with IV-H1N1 manifesting preference to alpha2,3 linkage. In contrast, linear alpha2,3 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,3-GalNAc, was not correlated with enhanced interaction between rNKp46 and IV-H1N1 with preference to alpha2,3 linkage. Branched alpha2,3 and alpha2,6 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,3[Neu5NAcalpha2,6]GalNAc, competently mediate the interaction of rNKp46 with IV-H1N1 manifesting preference to alpha2,6 linkage. Previous viral HA-binding specificity studies were performed with glycopolymer-conjugates, free synthetic sialyl oligosaccharides and sialidase-treated cells. This study shed a light on the O-glycan sequences involved in the interaction of glycoprotein and viral hemagglutinins and may help in the design of inhibitory agents to hemagglutinin for influenza treatment.
PMID: 20147410 [PubMed - as supplied by publisher]
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7. J Virol. 2010 Feb 10. [Epub ahead of print]
NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus.
Mendelson M, Tekoah Y, Zilka A, Gershoni-Yahalom O, Gazit R, Achdut H, Bovin NV, Segman-Meningher T, Mandelboim M, Mandelboim O, David A, Porgador A. - The Shraga Segal Department of Microbiology and Immunology and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, Israel; Center for Glycobiology, Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow GSP-7, 117997, Russia; Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer Israel; The Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Natural killer (NK) cells serve as a crucial first line defense against tumors and virus-infected cells. We previously showed that lysis of influenza virus (IV)-infected cells is mediated by the interaction between the NK receptor, NKp46, and the IV-hemagglutinin type 1 expressed by the infected cells. This interaction requires the presence of sialyl groups on the NKp46-T225-O-glycoforms. In the current study we analyzed the O-glycan sequences imperative for the interaction between recombinant NKp46 (rNKp46) and IV-H1N1 strains. We first showed that rNKp46 binding to IV-H1N1 is not mediated by a glycoform unique to the T225 site. We then characterized the O-glycan sequences that mediate the interaction of rNKp46 and IV-H1N1; we employed rNKp46s with dissimilar glycosylation pattern and IV-H1N1 strains with different preference to sialic acid alpha2,3 and alpha2,6 linkages. Branched alpha2,3 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,4-GlcNAcbeta1,6[Neu5NAcalpha2,3-Galbeta1,3]GalNAc, competently mediate the interaction of rNKp46 with IV-H1N1 manifesting preference to alpha2,3 linkage. In contrast, linear alpha2,3 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,3-GalNAc, was not correlated with enhanced interaction between rNKp46 and IV-H1N1 with preference to alpha2,3 linkage. Branched alpha2,3 and alpha2,6 sialylated O-glycoform, Neu5NAcalpha2,3-Galbeta1,3[Neu5NAcalpha2,6]GalNAc, competently mediate the interaction of rNKp46 with IV-H1N1 manifesting preference to alpha2,6 linkage. Previous viral HA-binding specificity studies were performed with glycopolymer-conjugates, free synthetic sialyl oligosaccharides and sialidase-treated cells. This study shed a light on the O-glycan sequences involved in the interaction of glycoprotein and viral hemagglutinins and may help in the design of inhibitory agents to hemagglutinin for influenza treatment.
PMID: 20147410 [PubMed - as supplied by publisher]
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