Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract
Ferrets are widely used as animal models for studying influenza A viral pathogenesis and transmissibility. Human-adapted influenza A viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasa...
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/71238 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0001-9307-6116 |
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| author | Jayaraman, Akila Chandrasekaran, Aarthi Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Fox, James G |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Jayaraman, Akila Chandrasekaran, Aarthi Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Fox, James G |
| author_sort | Jayaraman, Akila |
| collection | MIT |
| description | Ferrets are widely used as animal models for studying influenza A viral pathogenesis and transmissibility. Human-adapted influenza A viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. Viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specifically recognized by influenza A virus hemagglutinin (HA), a glycoprotein on viral surface. It is generally known that upper respiratory tract of humans and ferrets predominantly express α2→6 sialylated glycan receptors. However much less is known about the fine structure of these glycan receptors and their distribution in different regions of the ferret respiratory tract. In this study, we characterize distribution of glycan receptors going beyond terminal sialic acid linkage in the cranial and caudal regions of the ferret trachea (upper respiratory tract) and lung hilar region (lower respiratory tract) by multiplexing use of various plant lectins and human-adapted HAs to stain these tissue sections. Our findings show that the sialylated glycan receptors recognized by human-adapted HAs are predominantly distributed in submucosal gland of lung hilar region as a part of O-linked glycans. Our study has implications in understanding influenza A viral pathogenesis in ferrets and also in employing ferrets as animal models for developing therapeutic strategies against influenza. |
| first_indexed | 2024-09-23T12:51:53Z |
| format | Article |
| id | mit-1721.1/71238 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:51:53Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/712382022-10-01T11:37:04Z Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract Jayaraman, Akila Chandrasekaran, Aarthi Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Fox, James G Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Singapore-MIT Alliance in Research and Technology (SMART) Koch Institute for Integrative Cancer Research at MIT Fox, James G. Jayaraman, Akila Chandrasekaran, Aarthi Viswanathan, Karthik Raman, Rahul Fox, James G. Sasisekharan, Ram Ferrets are widely used as animal models for studying influenza A viral pathogenesis and transmissibility. Human-adapted influenza A viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. Viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specifically recognized by influenza A virus hemagglutinin (HA), a glycoprotein on viral surface. It is generally known that upper respiratory tract of humans and ferrets predominantly express α2→6 sialylated glycan receptors. However much less is known about the fine structure of these glycan receptors and their distribution in different regions of the ferret respiratory tract. In this study, we characterize distribution of glycan receptors going beyond terminal sialic acid linkage in the cranial and caudal regions of the ferret trachea (upper respiratory tract) and lung hilar region (lower respiratory tract) by multiplexing use of various plant lectins and human-adapted HAs to stain these tissue sections. Our findings show that the sialylated glycan receptors recognized by human-adapted HAs are predominantly distributed in submucosal gland of lung hilar region as a part of O-linked glycans. Our study has implications in understanding influenza A viral pathogenesis in ferrets and also in employing ferrets as animal models for developing therapeutic strategies against influenza. Singapore-MIT Alliance for Research and Technology 2012-06-27T21:23:54Z 2012-06-27T21:23:54Z 2012-02 2011-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/71238 Jayaraman, Akila et al. “Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract.” Ed. Cheryl A. Stoddart. PLoS ONE 7.2 (2012): e27517. Web. 27 June 2012. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1371/journal.pone.0027517 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Jayaraman, Akila Chandrasekaran, Aarthi Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Fox, James G Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title | Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title_full | Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title_fullStr | Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title_full_unstemmed | Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title_short | Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract |
| title_sort | decoding the distribution of glycan receptors for human adapted influenza a viruses in ferret respiratory tract |
| url | http://hdl.handle.net/1721.1/71238 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0001-9307-6116 |
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