Influenza hemagglutinin H3 - Revision history

Gillian Air: /* Biological roles of GBP-ligand interaction */

2011-04-19T22:45:53Z

Biological roles of GBP-ligand interaction

Gillian Air: /* Carbohydrate ligands */

2011-04-19T22:38:47Z

Carbohydrate ligands

Gillian Air: /* Cellular expression of GBP and ligands */

2011-04-19T18:54:11Z

Cellular expression of GBP and ligands

Gillian Air: /* Biosynthesis of ligands */

2011-04-13T04:40:35Z

Biosynthesis of ligands

Gillian Air: /* Biosynthesis of ligands */

2011-04-13T04:12:22Z

Biosynthesis of ligands

Gillian Air: /* Biosynthesis of ligands */

2011-04-09T21:48:59Z

Biosynthesis of ligands

Gillian Air: /* Biosynthesis of ligands */

2011-04-09T21:46:37Z

Biosynthesis of ligands

Carole Weaver: /* Related GBPs */

2011-03-22T18:21:40Z

Related GBPs

Carole Weaver: /* Knockout mouse lines */

2011-03-22T18:14:32Z

Knockout mouse lines

Ian Wilson: /* Acknowledgements */

2010-10-17T03:06:37Z

Acknowledgements

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 === Biological roles of GBP-ligand interaction ===
-Sialylated glycans on the surface of cells lining the respiratory tract serve to capture virus to initiate infection. Glycan array analyses have confirmed that human influenza viruses such as those carrying the H3 HA bind only to structures with NeuAc&alpha;2-6 and avian isolates bind only to structures containing NeuAc&alpha;2-3. The role of this GBP-glycan interaction in initiating endocytosis and replication is still unclear.
+Sialylated glycans on the surface of cells lining the respiratory tract serve to capture virus to initiate infection. Glycan array analyses have confirmed that human influenza viruses such as those carrying the H3 HA bind only to structures with NeuAc&alpha;2-6 and avian isolates bind only to structures containing NeuAc&alpha;2-3. The role of this GBP-glycan interaction in initiating endocytosis is still unclear, but in the low pH of the endosomal compartment, the HA undergoes a large conformational change <ref>Bullough et al “Structure of influenza hemagglutinin at the pH of membrane fusion”. Nature 371: 37-43 (1994)</ref> that brings about fusion of the viral membrane with the cell membrane so that viral nucleocapsids are released, enter the nucleus and initiate viral transcription and replication.
 == CFG resources used in investigations ==

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 === Carbohydrate ligands ===
-Ligands for H3 hemagglutinin are sialylated glycans. The H3 hemagglutinin of human viruses (subtype H3N2) binds to N-acetylneuraminic acid linked &alpha;2-6 to galactose, sometimes N-acetylgalactosamine. Glycan array analyses indicate that human influenza viruses such as those carrying the H3 HA bind only to structures with NeuAc&alpha;2-6 and avian isolates bind only to structures containing NeuAc&alpha;2-3. Recent human H3 HAs have shown variation in their specificity of binding downstream sugars.<ref>Gulati S, Smith DF, Air GM. Deletions of neuraminidase and resistance to oseltamivir may be a consequence of restricted receptor specificity in recent H3N2 influenza viruses. Virology J 2009;6(22).</ref>
+Ligands for H3 hemagglutinin are sialylated glycans. The H3 hemagglutinin of human viruses (subtype H3N2) binds to N-acetylneuraminic acid linked &alpha;2-6 to galactose, sometimes N-acetylgalactosamine. Glycan array analyses indicate that human influenza viruses such as those carrying the H3 HA bind only to structures with NeuAc&alpha;2-6 and avian isolates bind only to structures containing NeuAc&alpha;2-3. Recent human H3 HAs have shown variation in their specificity of binding downstream sugars.<ref>Gulati S, Smith DF, Air GM. Deletions of neuraminidase and resistance to oseltamivir may be a consequence of restricted receptor specificity in recent H3N2 influenza viruses. Virology J 2009;6(22) </ref>. Occasionally human H3N2 HAs bind to 2-3 linked sialic acids, such as sialyl-Lewis x <ref>Stevens, J., Chen, L.-M., Carney, P.J., Garten, R., Foust, A., Le, J., Pokorny, B.A., Manojkumar, R., Silverman, J., Devis, R., Rhea, K., Xu, X., Bucher, D.J., Paulson, J.C., Paulson, J., Cox, N.J., Klimov, A., Donis, R.O., 2010. Receptor specificity of influenza A H3N2 viruses isolated in mammalian cells and embryonated chicken eggs. Journal of Virology 84, 8287-8299.</ref>
 <br>
 [[File:H3binding2.png]]

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 === Cellular expression of GBP and ligands ===
-HA is expressed on the surface of influenza virus infected cells before being budded out into progeny virions. H3N2 viruses infect the respiratory tract of humans and birds; in birds they may also infect the gut epithelia. H3N2 viruses infect very few continuous cell lines. Madin-Darby canine kidney cells are most commonly used. Non-permissive cell lines may take up virus efficiently, replicate RNA and express HA on the cell surface but do not bud new virus particles <ref>Kumari K, Gulati S, Smith DF, Gulati U, Cummings RD, Air GM. Receptor binding specificity of recent human H3N2 influenza viruses. Virol J 2007;4(42):1-12.</ref>.
+HA is expressed on the surface of influenza virus infected cells before being budded out into progeny virions. H3N2 viruses infect the respiratory tract of humans and birds; in birds they may also infect the gut epithelia. Using MAA and SNA lectins, the upper respiratory tract appears to have more 2-6 linked sialic acid while 2-3 sialic acid appears more abundant in the lungs, but relationship between the different specificities of H3N2 HAs and the cell types infected remains unclear <ref> NICHOLLS, J., CHAN, R., Russell, R., Air, G., PEIRIS, J., 2008. Evolving complexities of influenza virus and its receptors. Trends in Microbiology 16, 149-157. </ref>. H3N2 viruses infect very few continuous cell lines. Madin-Darby canine kidney cells are most commonly used. Non-permissive cell lines may take up virus efficiently, replicate RNA and express HA on the cell surface but do not bud new virus particles <ref>Kumari K, Gulati S, Smith DF, Gulati U, Cummings RD, Air GM. Receptor binding specificity of recent human H3N2 influenza viruses. Virol J 2007;4(42):1-12.</ref>.
 === Biosynthesis of ligands ===

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 === Biosynthesis of ligands ===
 <br>
 === Structure ===

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 === Biosynthesis of ligands ===
 <br>
-Sialylated glycoproteins or glycolipids recognized by human influenza hemagglutinin H3 are synthesized by host cells. The H3 hemagglutinin shows considerable diversity in binding but with rare exceptions the sialic acid is attached 2-6 to the next sugar on structures that are mostly typical of N-linked glycans on proteins. The enzymes required for biosynthesis of the type 2 poly N-acetyllactosamine chains and modification with sialic acid or with sialic acid and fucose, have been defined ([http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/geMolecule.jsp?slideNumber=slide7][poly N-acetyllactosamine extension biosynthesis]).
+Sialylated glycoproteins or glycolipids recognized by human influenza hemagglutinin H3 are synthesized by host cells. The H3 hemagglutinin shows considerable diversity in binding but with rare exceptions the sialic acid is attached 2-6 to the next sugar on structures that are mostly typical of N-linked glycans on proteins. The enzymes required for biosynthesis of the type 2 poly N-acetyllactosamine chains and modification with sialic acid or with sialic acid and fucose, have been defined ([http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/geMolecule.jsp?slideNumber=slide7][poly N-acetyllactosamine extension biosynthesis]). The sialyltransferases that generate ligands for most H3 subtype hemagglutinins are ST6Gal1, ST6GalII, ST6GalNAc1, ST6GalNAcII, ST6GalNAcIV.
 === Structure ===

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 == Related GBPs ==
-Influenza virus HAs of other serotype H1, H2, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16 and type B. Type A subtypes H1, H2, H5, H6, H7, and H9 are all being actively investigated by CFG investigators for their potential to jump to humans and type B for its failure to spread in non-human species.
+Influenza virus HAs of other serotype H1, H2, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16 and type B. Type A subtypes H1, H2, H5, H6, H7, and H9 are all being actively investigated by CFG investigators for their potential to jump to humans and type B for its failure to spread in non-human species. CFG data for many of these subtypes are available in the [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=hemagglutinin&maxresults=20 CFG database search results for "hemagglutinin."]
 == References ==

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 === Knockout mouse lines ===
-Unfortunately the mouse is a very poor model of influenza infection. Some viruses with H3 HA infect mice quite readily, but do not cause a human-like disease. This means that studies of infection and transmission of H3N2 influenza viruses in SiaT knockout mice are difficult to translate to the human disease. HOwever, studies were done using a mouse-adapted virus <ref> Glaser L, Conenello G, Paulson J, Palese P. Effective replication of human influenza viruses in mice lacking a major alpha2,6 sialyltransferase. Virus Res. 2007 Jun;126(1-2):9-18.</ref>
+Unfortunately the mouse is a very poor model of influenza infection. Some viruses with H3 HA infect mice quite readily, but do not cause a human-like disease. This means that studies of infection and transmission of H3N2 influenza viruses in SiaT knockout mice are difficult to translate to the human disease. However, studies were done using a mouse-adapted virus <ref> Glaser L, Conenello G, Paulson J, Palese P. Effective replication of human influenza viruses in mice lacking a major alpha2,6 sialyltransferase. Virus Res. 2007 Jun;126(1-2):9-18.</ref>
 === Glycan array ===

← Older revision		Revision as of 03:06, 17 October 2010
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	== Acknowledgements ==		== Acknowledgements ==
−	The CFG is grateful to the following PIs for their contributions to this wiki page: Gillian Air, James Paulson	+	The CFG is grateful to the following PIs for their contributions to this wiki page: Gillian Air, James Paulson, Ian Wilson