Giuseppe
Emeritus
Glycans on influenza hemagglutinin affect receptor binding and immune response (Proc Natl Acad Sci USA, abstract, edited)
Glycans on influenza hemagglutinin affect receptor binding and immune response
* This article contains supporting information online at www.pnas.org/cgi/content/full/0909696106/DCSupplemental
1. Cheng-Chi Wang a,b,1, 2. Juine-Ruey Chen a,c,1, 3. Yung-Chieh Tseng a, 4. Che-Hsiung Hsu a,d,e, 5. Yu-Fu Hung a, 6. Shih-Wei Chen a, 7. Chin-Mei Chen f, 8. Kay-Hooi Khoo f, 9. Ting-Jen Cheng a, 10. Yih-Shyun E. Cheng a, 11. Jia-Tsrong Jan a, 12. Chung-Yi Wu a, 13. Che Ma a,2 and 14. Chi-Huey Wong a,2
- Author Affiliations
1. aGenomics Research Center,
2. dChemical Biology and Molecular Biophysics, Taiwan International Graduate Program, and
3. fInstitute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan;
4. bInstitute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan;
5. cInstitute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan; and
6. eInstitute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan
1. Contributed by Chi-Huey Wong, September 1, 2009 2.
↵1C.-C.W. and J.-R.C. contributed equally to this work.
(received for review August 3, 2009)
Abstract
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.
* flu vaccine * glycan binding * glycosylation
Footnotes *
2To whom correspondence may be addressed. E-mail: cma@gate.sinica.edu.tw or chwong@gate.sinica.edu.tw
* Author contributions: C.-Y.W., C.M., and C.-H.W. designed research; C.-C.W., J.-R.C., Y.-C.T., C.-H.H., Y.-F.H., S.-W.C., C.-M.C., K.-H.K., and J.-T.J. performed research; T.-J.C. and Y.-S.E.C. contributed new reagents/analytic tools; C.-C.W. and J.-R.C. analyzed data; and C.-C.W., J.-R.C., C.-Y.W., C.M., and C.-H.W. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at www.pnas.org/cgi/content/full/0909696106/DCSupplemental
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<cite cite="http://www.pnas.org/content/106/43/18137.short?rss=1">Glycans on influenza hemagglutinin affect receptor binding and immune response ? PNAS</cite>* This article contains supporting information online at www.pnas.org/cgi/content/full/0909696106/DCSupplemental
1. Cheng-Chi Wang a,b,1, 2. Juine-Ruey Chen a,c,1, 3. Yung-Chieh Tseng a, 4. Che-Hsiung Hsu a,d,e, 5. Yu-Fu Hung a, 6. Shih-Wei Chen a, 7. Chin-Mei Chen f, 8. Kay-Hooi Khoo f, 9. Ting-Jen Cheng a, 10. Yih-Shyun E. Cheng a, 11. Jia-Tsrong Jan a, 12. Chung-Yi Wu a, 13. Che Ma a,2 and 14. Chi-Huey Wong a,2
- Author Affiliations
1. aGenomics Research Center,
2. dChemical Biology and Molecular Biophysics, Taiwan International Graduate Program, and
3. fInstitute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan;
4. bInstitute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan;
5. cInstitute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan; and
6. eInstitute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan
1. Contributed by Chi-Huey Wong, September 1, 2009 2.
↵1C.-C.W. and J.-R.C. contributed equally to this work.
(received for review August 3, 2009)
Abstract
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.
* flu vaccine * glycan binding * glycosylation
Footnotes *
2To whom correspondence may be addressed. E-mail: cma@gate.sinica.edu.tw or chwong@gate.sinica.edu.tw
* Author contributions: C.-Y.W., C.M., and C.-H.W. designed research; C.-C.W., J.-R.C., Y.-C.T., C.-H.H., Y.-F.H., S.-W.C., C.-M.C., K.-H.K., and J.-T.J. performed research; T.-J.C. and Y.-S.E.C. contributed new reagents/analytic tools; C.-C.W. and J.-R.C. analyzed data; and C.-C.W., J.-R.C., C.-Y.W., C.M., and C.-H.W. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at www.pnas.org/cgi/content/full/0909696106/DCSupplemental
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