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...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
2013
|
| Online Access: | http://hdl.handle.net/1721.1/82661 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
| _version_ | 1826212982902751232 |
|---|---|
| author | Viswanathan, Karthik Chandrasekaran, Aarthi Srinivasan, Aravind Raman, Rahul Sasisekharan, V. Sasisekharan, Ram |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Viswanathan, Karthik Chandrasekaran, Aarthi Srinivasan, Aravind Raman, Rahul Sasisekharan, V. Sasisekharan, Ram |
| author_sort | Viswanathan, Karthik |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:41:15Z |
| format | Article |
| id | mit-1721.1/82661 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:41:15Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | mit-1721.1/826612022-09-29T15:29:27Z Glycans as receptors for influenza pathogenesis Viswanathan, Karthik Chandrasekaran, Aarthi Srinivasan, Aravind Raman, Rahul Sasisekharan, V. Sasisekharan, Ram Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. School of Engineering Viswanathan, Karthik Chandrasekaran, Aarthi Srinivasan, Aravind Raman, Rahul Sasisekharan, Ram Sasisekharan, V. 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. National Institute of General Medical Sciences (U.S.) (Glue Grant U54 GM62116) National Institutes of Health (U.S.) (Grant GM57073) Singapore-MIT Alliance for Research and Technology 2013-12-06T15:53:25Z 2013-12-06T15:53:25Z 2010-08 Article http://purl.org/eprint/type/JournalArticle 0282-0080 1573-4986 http://hdl.handle.net/1721.1/82661 Viswanathan, Karthik, Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, V. Sasisekharan, and Ram Sasisekharan. “Glycans as receptors for influenza pathogenesis.” Glycoconjugate Journal 27, no. 6 (August 24, 2010): 561-570. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1007/s10719-010-9303-4 Glycoconjugate Journal http://creativecommons.org/licenses/by/3.0/ application/pdf PMC |
| spellingShingle | Viswanathan, Karthik Chandrasekaran, Aarthi Srinivasan, Aravind Raman, Rahul Sasisekharan, V. Sasisekharan, Ram Glycans as receptors for influenza pathogenesis |
| title | Glycans as receptors for influenza pathogenesis |
| title_full | Glycans as receptors for influenza pathogenesis |
| title_fullStr | Glycans as receptors for influenza pathogenesis |
| title_full_unstemmed | Glycans as receptors for influenza pathogenesis |
| title_short | Glycans as receptors for influenza pathogenesis |
| title_sort | glycans as receptors for influenza pathogenesis |
| url | http://hdl.handle.net/1721.1/82661 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
| work_keys_str_mv | AT viswanathankarthik glycansasreceptorsforinfluenzapathogenesis AT chandrasekaranaarthi glycansasreceptorsforinfluenzapathogenesis AT srinivasanaravind glycansasreceptorsforinfluenzapathogenesis AT ramanrahul glycansasreceptorsforinfluenzapathogenesis AT sasisekharanv glycansasreceptorsforinfluenzapathogenesis AT sasisekharanram glycansasreceptorsforinfluenzapathogenesis |