Glycans as receptors for influenza pathogenesis

Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acα2-3Gal linked (α2-3) to Neu5Acα2-6Gal linked (α2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of α2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to α2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.

[1]  Yi Guan,et al.  Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia , 2006, Nature Medicine.

[2]  Yoshihiro Kawaoka,et al.  Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals , 2000, Journal of Virology.

[3]  D. J. Stevens,et al.  Avian and human receptor binding by hemagglutinins of influenza A viruses , 2006, Glycoconjugate Journal.

[4]  H. Faillard,et al.  [Enzymatic effect of the influenza virus]. , 1955, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[5]  Yoshihiro Kawaoka,et al.  Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses , 2000, Journal of Virology.

[6]  R. Schauer,et al.  Structure, function and metabolism of sialic acids , 1998, Cellular and Molecular Life Sciences CMLS.

[7]  J. Skehel,et al.  X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Nicolai Bovin,et al.  Receptor specificity of influenza viruses from birds and mammals: new data on involvement of the inner fragments of the carbohydrate chain. , 2005, Virology.

[9]  Peter H. Seeberger,et al.  Synthesis and medical applications of oligosaccharides , 2007, Nature.

[10]  G. K. Hirst.  THE AGGLUTINATION OF RED CELLS BY ALLANTOIC FLUID OF CHICK EMBRYOS INFECTED WITH INFLUENZA VIRUS. , 1941, Science.

[11]  G. Wiederschain,et al.  Essentials of glycobiology , 2009, Biochemistry (Moscow).

[12]  David E. Swayne,et al.  Isolation and Characterization of Avian Influenza Viruses, Including Highly Pathogenic H5N1, from Poultry in Live Bird Markets in Hanoi, Vietnam, in 2001 , 2005, Journal of Virology.

[13]  Richard D. Cummings,et al.  Quantifiable fluorescent glycan microarrays , 2007, Glycoconjugate Journal.

[14]  H. Klenk,et al.  Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors , 2003, Journal of Virology.

[15]  J. Paulson,et al.  Sialyloligosaccharides of the respiratory epithelium in the selection of human influenza virus receptor specificity. , 1990, Acta histochemica. Supplementband.

[16]  Constance Schultsz,et al.  Avian influenza A (H5N1) in 10 patients in Vietnam. , 2004, The New England journal of medicine.

[17]  Ya Ha,et al.  X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus. , 2003, Virology.

[18]  Chi‐Huey Wong,et al.  Chemoenzymatic synthesis of oligosaccharides and glycoproteins. , 2004, Trends in biochemical sciences.

[19]  Chih-Jen Wei,et al.  Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity , 2007, Science.

[20]  N V Bovin,et al.  Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenza B viruses share a common high binding affinity for 6'-sialyl(N-acetyllactosamine). , 1997, Virology.

[21]  M B Eisen,et al.  Binding of the influenza A virus to cell-surface receptors: structures of five hemagglutinin-sialyloligosaccharide complexes determined by X-ray crystallography. , 1997, Virology.

[22]  R. Webster,et al.  Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model , 2007, Journal of Virology.

[23]  N. Bovin,et al.  Human influenza virus recognition of sialyloligosaccharides , 1995, FEBS letters.

[24]  G. Werner,et al.  Studies on the enzymatic properties of influenza viruses. I. The action of influenza B virus and RDE on the hemagglutinin inhibitor of human meconium. , 1957, Virology.

[25]  A. Gottschalk,et al.  Product of Interaction between Influenza Virus Enzyme and Ovomucin , 1949, Nature.

[26]  T. Tumpey,et al.  Characterization of Highly Pathogenic H5N1 Avian Influenza A Viruses Isolated from South Korea , 2005, Journal of Virology.

[27]  J. Skehel,et al.  Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. , 2000, Annual review of biochemistry.

[28]  P. Bóhm,et al.  [Cleavage of N-acetylneuraminic acid from serum by the receptor-destroying enzyme from Vibrio cholerae]. , 1957, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[29]  Yoshihiro Kawaoka,et al.  Avian flu: Influenza virus receptors in the human airway , 2006, Nature.

[30]  I. Wilson,et al.  Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution , 1981, Nature.

[31]  M. Matrosovich,et al.  A solid-phase enzyme-linked assay for influenza virus receptor-binding activity. , 1992, Journal of virological methods.

[32]  J. Taubenberger,et al.  Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. J. Stevens,et al.  The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin , 2004, Science.

[34]  I. Wilson,et al.  Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. , 2008, Journal of molecular biology.

[35]  David E. Swayne,et al.  Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus , 2005, Science.

[36]  J. Paulson,et al.  Resialylated erythrocytes for assessment of the specificity of sialyloligosaccharide binding proteins. , 1987, Methods in enzymology.

[37]  C. Bewley.  Illuminating the switch in influenza viruses , 2008, Nature Biotechnology.

[38]  Gabriele Neumann,et al.  Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic , 2006, Emerging infectious diseases.

[39]  A. Varki,et al.  Diversity in cell surface sialic acid presentations: implications for biology and disease , 2007, Laboratory Investigation.

[40]  Ian A. Wilson,et al.  Glycan microarray technologies: tools to survey host specificity of influenza viruses , 2006, Nature Reviews Microbiology.

[41]  L Döhner,et al.  [Genetics of influenza viruses]. , 1978, Archiv fur experimentelle Veterinarmedizin.

[42]  Chi-Huey Wong,et al.  Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  David E. Swayne,et al.  A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission , 2007, Science.

[44]  R. Webster,et al.  The Surface Glycoproteins of H5 Influenza Viruses Isolated from Humans, Chickens, and Wild Aquatic Birds Have Distinguishable Properties , 1999, Journal of Virology.

[45]  Evaluation of a High-Pathogenicity H5N1 Avian Influenza A Virus Isolated from Duck Meat , 2003, Avian diseases.

[46]  R. Sasisekharan,et al.  Cooperativity in glycan-protein interactions. , 2007, Chemistry & biology.

[47]  Rahul Raman,et al.  Glycomics approach to structure-function relationships of glycosaminoglycans. , 2006, Annual review of biomedical engineering.

[48]  M. Götte,et al.  Functions of cell surface heparan sulfate proteoglycans. , 1999, Annual review of biochemistry.

[49]  A. Srinivasan,et al.  Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses , 2008, Proceedings of the National Academy of Sciences.

[50]  Yoshihiro Kawaoka,et al.  Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential , 1998, Journal of Virology.

[51]  P. Palese,et al.  Influenza: old and new threats , 2004, Nature Medicine.

[52]  R. Krug,et al.  The Influenza Viruses , 2011, The Viruses.

[53]  E. Holmes,et al.  The evolution of epidemic influenza , 2007, Nature Reviews Genetics.

[54]  Nicolai V Bovin,et al.  Virology Journal BioMed Central , 2008 .

[55]  J. Paulson,et al.  Glycomics: an integrated systems approach to structure-function relationships of glycans , 2005, Nature Methods.

[56]  Lucy A. Perrone,et al.  Reconstruction of the 1918 pandemic influenza virus: how revealing the molecular secrets of the virus responsible for the worst pandemic in recorded history can guide our response to future influenza pandemics. , 2007, Infectious disorders drug targets.

[57]  Ian A. Wilson,et al.  Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus , 2006, Science.

[58]  A. Lander,et al.  Mechanisms Underlying Preferential Assembly of Heparan Sulfate on Glypican-1* , 2001, The Journal of Biological Chemistry.

[59]  R. Webster,et al.  Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. , 1994, Virology.

[60]  Ola Blixt,et al.  Chemoenzymatic synthesis of glycan libraries. , 2006, Methods in enzymology.

[61]  David F. Smith,et al.  Receptor binding specificity of recent human H3N2 influenza viruses , 2007, Virology Journal.

[62]  E. Holmes,et al.  Host Species Barriers to Influenza Virus Infections , 2006, Science.

[63]  Jeffery K. Taubenberger,et al.  Characterization of the 1918 influenza virus polymerase genes , 2005, Nature.

[64]  A. J. Bourne,et al.  Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses , 2007, Respiratory research.

[65]  N. Cox,et al.  Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals , 2005, Journal of Virology.

[66]  N. Cox,et al.  Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model , 2006, Proceedings of the National Academy of Sciences.

[67]  J. Skehel,et al.  H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes. , 2004, Virology.

[68]  David J. Stevens,et al.  Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors , 2006, Nature.

[69]  J. Skehel,et al.  The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. , 1987, Annual review of biochemistry.

[70]  A. Srinivasan,et al.  Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin , 2008, Nature Biotechnology.

[71]  J. Paulson,et al.  Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. , 1983, Virology.