A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets
The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/65575 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 |
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| author | Jayaraman, Akila Pappas, Claudia Raman, Rahul Belser, Jessica A. Viswanathan, Karthik Tumpey, Terrence M. Sasisekharan, Ram Shriver, Zachary H. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Jayaraman, Akila Pappas, Claudia Raman, Rahul Belser, Jessica A. Viswanathan, Karthik Tumpey, Terrence M. Sasisekharan, Ram Shriver, Zachary H. |
| author_sort | Jayaraman, Akila |
| collection | MIT |
| description | The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA) to α2→6 sialylated glycan receptors (human receptors). Here we report that a single point mutation (Ile219→Lys; a base pair change) in the glycan receptor-binding site (RBS) of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics) transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses. |
| first_indexed | 2024-09-23T14:48:42Z |
| format | Article |
| id | mit-1721.1/65575 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:48:42Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/655752022-10-01T22:36:47Z A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets Jayaraman, Akila Pappas, Claudia Raman, Rahul Belser, Jessica A. Viswanathan, Karthik Tumpey, Terrence M. Sasisekharan, Ram Shriver, Zachary H. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Singapore-MIT Alliance in Research and Technology (SMART) Koch Institute for Integrative Cancer Research at MIT Sasisekharan, Ram Sasisekharan, Ram Jayaraman, Akila Raman, Rahul Viswanathan, Karthik Shriver, Zachary The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA) to α2→6 sialylated glycan receptors (human receptors). Here we report that a single point mutation (Ile219→Lys; a base pair change) in the glycan receptor-binding site (RBS) of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics) transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses. 2011-08-31T18:43:35Z 2011-08-31T18:43:35Z 2011-03 2010-11 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/65575 Jayaraman, Akila et al. “A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets.” Ed. Elankumaran Subbiah. PLoS ONE 6.3 (2011) : e17616. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1371/journal.pone.0017616 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Jayaraman, Akila Pappas, Claudia Raman, Rahul Belser, Jessica A. Viswanathan, Karthik Tumpey, Terrence M. Sasisekharan, Ram Shriver, Zachary H. A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title | A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title_full | A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title_fullStr | A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title_full_unstemmed | A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title_short | A Single Base-Pair Change in 2009 H1N1 Hemagglutinin Increases Human Receptor Affinity and Leads to Efficient Airborne Viral Transmission in Ferrets |
| title_sort | single base pair change in 2009 h1n1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets |
| url | http://hdl.handle.net/1721.1/65575 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 |
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