Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread.
It is generally accepted that human influenza viruses bind glycans containing sialic acid linked α2-6 to the next sugar, that avian influenza viruses bind glycans containing the α2-3 linkage, and that mutations that change the binding specificity might change the host tropism. We noted that human H3...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3689742?pdf=render |
| _version_ | 1818017231424978944 |
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| author | Shelly Gulati David F Smith Richard D Cummings Robert B Couch Sara B Griesemer Kirsten St George Robert G Webster Gillian M Air |
| author_facet | Shelly Gulati David F Smith Richard D Cummings Robert B Couch Sara B Griesemer Kirsten St George Robert G Webster Gillian M Air |
| author_sort | Shelly Gulati |
| collection | DOAJ |
| description | It is generally accepted that human influenza viruses bind glycans containing sialic acid linked α2-6 to the next sugar, that avian influenza viruses bind glycans containing the α2-3 linkage, and that mutations that change the binding specificity might change the host tropism. We noted that human H3N2 viruses showed dramatic differences in their binding specificity, and so we embarked on a study of representative human H3N2 influenza viruses, isolated from 1968 to 2012, that had been isolated and minimally passaged only in mammalian cells, never in eggs. The 45 viruses were grown in MDCK cells, purified, fluorescently labeled and screened on the Consortium for Functional Glycomics Glycan Array. Viruses isolated in the same season have similar binding specificity profiles but the profiles show marked year-to-year variation. None of the 610 glycans on the array (166 sialylated glycans) bound to all viruses; the closest was Neu5Acα2-6(Galβ1-4GlcNAc)3 in either a linear or biantennary form, that bound 42 of the 45 viruses. The earliest human H3N2 viruses preferentially bound short, branched sialylated glycans while recent viruses bind better to long polylactosamine chains terminating in sialic acid. Viruses isolated in 1996, 2006, 2010 and 2012 bind glycans with α2-3 linked sialic acid; for 2006, 2010 and 2012 viruses this binding was inhibited by oseltamivir, indicating binding of α2-3 sialylated glycans by neuraminidase. More significantly, oseltamivir inhibited virus entry of 2010 and 2012 viruses into MDCK cells. All of these viruses were representative of epidemic strains that spread around the world, so all could infect and transmit between humans with high efficiency. We conclude that the year-to-year variation in receptor binding specificity is a consequence of amino acid sequence changes driven by antigenic drift, and that viruses with quite different binding specificity and avidity are equally fit to infect and transmit in the human population. |
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| format | Article |
| id | doaj.art-6b5856248bdf4def8c5e6832bdba60d3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T07:23:28Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6b5856248bdf4def8c5e6832bdba60d32022-12-22T02:06:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6632510.1371/journal.pone.0066325Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread.Shelly GulatiDavid F SmithRichard D CummingsRobert B CouchSara B GriesemerKirsten St GeorgeRobert G WebsterGillian M AirIt is generally accepted that human influenza viruses bind glycans containing sialic acid linked α2-6 to the next sugar, that avian influenza viruses bind glycans containing the α2-3 linkage, and that mutations that change the binding specificity might change the host tropism. We noted that human H3N2 viruses showed dramatic differences in their binding specificity, and so we embarked on a study of representative human H3N2 influenza viruses, isolated from 1968 to 2012, that had been isolated and minimally passaged only in mammalian cells, never in eggs. The 45 viruses were grown in MDCK cells, purified, fluorescently labeled and screened on the Consortium for Functional Glycomics Glycan Array. Viruses isolated in the same season have similar binding specificity profiles but the profiles show marked year-to-year variation. None of the 610 glycans on the array (166 sialylated glycans) bound to all viruses; the closest was Neu5Acα2-6(Galβ1-4GlcNAc)3 in either a linear or biantennary form, that bound 42 of the 45 viruses. The earliest human H3N2 viruses preferentially bound short, branched sialylated glycans while recent viruses bind better to long polylactosamine chains terminating in sialic acid. Viruses isolated in 1996, 2006, 2010 and 2012 bind glycans with α2-3 linked sialic acid; for 2006, 2010 and 2012 viruses this binding was inhibited by oseltamivir, indicating binding of α2-3 sialylated glycans by neuraminidase. More significantly, oseltamivir inhibited virus entry of 2010 and 2012 viruses into MDCK cells. All of these viruses were representative of epidemic strains that spread around the world, so all could infect and transmit between humans with high efficiency. We conclude that the year-to-year variation in receptor binding specificity is a consequence of amino acid sequence changes driven by antigenic drift, and that viruses with quite different binding specificity and avidity are equally fit to infect and transmit in the human population.http://europepmc.org/articles/PMC3689742?pdf=render |
| spellingShingle | Shelly Gulati David F Smith Richard D Cummings Robert B Couch Sara B Griesemer Kirsten St George Robert G Webster Gillian M Air Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. PLoS ONE |
| title | Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. |
| title_full | Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. |
| title_fullStr | Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. |
| title_full_unstemmed | Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. |
| title_short | Human H3N2 Influenza Viruses Isolated from 1968 To 2012 Show Varying Preference for Receptor Substructures with No Apparent Consequences for Disease or Spread. |
| title_sort | human h3n2 influenza viruses isolated from 1968 to 2012 show varying preference for receptor substructures with no apparent consequences for disease or spread |
| url | http://europepmc.org/articles/PMC3689742?pdf=render |
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