Modular glycosphere assays for high-throughput functional characterization of influenza viruses
Background: The ongoing global efforts to control influenza epidemics and pandemics require high-throughput technologies to detect, quantify, and functionally characterize viral isolates. The 2009 influenza pandemic as well as the recent in-vitro selection of highly transmissible H5N1 variants have...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2013
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| Online Access: | http://hdl.handle.net/1721.1/80335 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 | Hobbie, Sven N. Viswanathan, Karthik Bachelet, Ido Aich, Udayanath Subramanian, Vidya Raman, Rahul 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 Hobbie, Sven N. Viswanathan, Karthik Bachelet, Ido Aich, Udayanath Subramanian, Vidya Raman, Rahul Sasisekharan, Ram Shriver, Zachary H. |
| author_sort | Hobbie, Sven N. |
| collection | MIT |
| description | Background:
The ongoing global efforts to control influenza epidemics and pandemics require high-throughput technologies to detect, quantify, and functionally characterize viral isolates. The 2009 influenza pandemic as well as the recent in-vitro selection of highly transmissible H5N1 variants have only increased existing concerns about emerging influenza strains with significantly enhanced human-to-human transmissibility. High-affinity binding of the virus hemagglutinin to human receptor glycans is a highly sensitive and stringent indicator of host adaptation and virus transmissibility. The surveillance of receptor-binding characteristics can therefore provide a strong additional indicator for the relative hazard imposed by circulating and newly emerging influenza strains.
Results:
Streptavidin-coated microspheres were coated with selected biotinylated glycans to mimic either human or avian influenza host-cell receptors. Such glycospheres were used to selectively capture influenza virus of diverse subtypes from a variety of samples. Bound virus was then detected by fluorescently labelled antibodies and analyzed by quantitative flow cytometry. Recombinant hemagglutinin, inactivated virus, and influenza virions were captured and analyzed with regards to receptor specificity over a wide range of analyte concentration. High-throughput analyses of influenza virus produced dose-response curves that allow for functional assessment of relative receptor affinity and thus transmissibility.
Conclusions:
Modular glycosphere assays for high-throughput functional characterization of influenza viruses introduce an important tool to augment the surveillance of clinical and veterinarian influenza isolates with regards to receptor specificity, host adaptation, and virus transmissibility. |
| first_indexed | 2024-09-23T13:29:35Z |
| format | Article |
| id | mit-1721.1/80335 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:29:35Z |
| publishDate | 2013 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/803352022-10-01T15:34:00Z Modular glycosphere assays for high-throughput functional characterization of influenza viruses Hobbie, Sven N. Viswanathan, Karthik Bachelet, Ido Aich, Udayanath Subramanian, Vidya Raman, Rahul Sasisekharan, Ram Shriver, Zachary H. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. School of Engineering Koch Institute for Integrative Cancer Research at MIT Viswanathan, Karthik Bachelet, Ido Aich, Udayanath Shriver, Zachary H. Subramanian, Vidya Raman, Rahul Sasisekharan, Ram Background: The ongoing global efforts to control influenza epidemics and pandemics require high-throughput technologies to detect, quantify, and functionally characterize viral isolates. The 2009 influenza pandemic as well as the recent in-vitro selection of highly transmissible H5N1 variants have only increased existing concerns about emerging influenza strains with significantly enhanced human-to-human transmissibility. High-affinity binding of the virus hemagglutinin to human receptor glycans is a highly sensitive and stringent indicator of host adaptation and virus transmissibility. The surveillance of receptor-binding characteristics can therefore provide a strong additional indicator for the relative hazard imposed by circulating and newly emerging influenza strains. Results: Streptavidin-coated microspheres were coated with selected biotinylated glycans to mimic either human or avian influenza host-cell receptors. Such glycospheres were used to selectively capture influenza virus of diverse subtypes from a variety of samples. Bound virus was then detected by fluorescently labelled antibodies and analyzed by quantitative flow cytometry. Recombinant hemagglutinin, inactivated virus, and influenza virions were captured and analyzed with regards to receptor specificity over a wide range of analyte concentration. High-throughput analyses of influenza virus produced dose-response curves that allow for functional assessment of relative receptor affinity and thus transmissibility. Conclusions: Modular glycosphere assays for high-throughput functional characterization of influenza viruses introduce an important tool to augment the surveillance of clinical and veterinarian influenza isolates with regards to receptor specificity, host adaptation, and virus transmissibility. Singapore-MIT Alliance for Research and Technology 2013-09-03T14:12:47Z 2013-09-03T14:12:47Z 2013-04 2012-11 2013-08-24T04:05:09Z Article http://purl.org/eprint/type/JournalArticle 1472-6750 http://hdl.handle.net/1721.1/80335 Hobbie, Sven N, Karthik Viswanathan, Ido Bachelet, Udayanath Aich, Zachary Shriver, Vidya Subramanian, Rahul Raman, and Ram Sasisekharan. “Modular glycosphere assays for high-throughput functional characterization of influenza viruses.” BMC Biotechnology 13, no. 1 (2013): 34 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 en http://dx.doi.org/10.1186/1472-6750-13-34 BMC Biotechnology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Sven N Hobbie et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Hobbie, Sven N. Viswanathan, Karthik Bachelet, Ido Aich, Udayanath Subramanian, Vidya Raman, Rahul Sasisekharan, Ram Shriver, Zachary H. Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title | Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title_full | Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title_fullStr | Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title_full_unstemmed | Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title_short | Modular glycosphere assays for high-throughput functional characterization of influenza viruses |
| title_sort | modular glycosphere assays for high throughput functional characterization of influenza viruses |
| url | http://hdl.handle.net/1721.1/80335 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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