Giuseppe
Emeritus
Proc Natl Acad Sci U S A. 2009 Oct 12. [Epub ahead of print]
Glycans on influenza hemagglutinin affect receptor binding and immune response.
Wang CC, Chen JR, Tseng YC, Hsu CH, Hung YF, Chen SW, Chen CM, Khoo KH, Cheng TJ, Cheng YS, Jan JT, Wu CY, Ma C, Wong CH. - Genomics Research Center, Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, and Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA glycoforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the biantennary glycan to the monoglycosylated HA glycoform. Antibodies raised against HA protein bearing only a single N-linked GlcNAc at each glycosylation site showed better binding affinity and neutralization activity against influenza subtypes than the fully glycosylated HAs elicited. Thus, removal of structurally nonessential glycans on viral surface glycoproteins may be a very effective and general approach for vaccine design against influenza and other human viruses.
PMID: 19822741 [PubMed - as supplied by publisher]
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Glycans on influenza hemagglutinin affect receptor binding and immune response.
Wang CC, Chen JR, Tseng YC, Hsu CH, Hung YF, Chen SW, Chen CM, Khoo KH, Cheng TJ, Cheng YS, Jan JT, Wu CY, Ma C, Wong CH. - Genomics Research Center, Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, and Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA glycoforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the biantennary glycan to the monoglycosylated HA glycoform. Antibodies raised against HA protein bearing only a single N-linked GlcNAc at each glycosylation site showed better binding affinity and neutralization activity against influenza subtypes than the fully glycosylated HAs elicited. Thus, removal of structurally nonessential glycans on viral surface glycoproteins may be a very effective and general approach for vaccine design against influenza and other human viruses.
PMID: 19822741 [PubMed - as supplied by publisher]
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