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Identification of critical residues of influenza neuraminidase in viral particle release

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journal contribution
posted on 26.05.2011, 00:00 by Jennifer R. Tisoncik, Ying Guo, Katie S. Cordero, Jia Yu, Jianwei Wang, Youjia Cao, Lijun Rong
BACKGROUND: Influenza neuraminidase (NA) is essential for virus release from its host cells and it is one of the targets for structure-based antiviral drug design. RESULTS: In this report, we established a pseudoviral particle release assay to study NA function, which is based on lentiviral particles pseudotyped with influenza glycoproteins HA and NA as a surrogate system. Through an extensive molecular analysis, we sought to characterize important residues governing NA function. We identified five residues of NA, 234, 241, 257, 286 and 345, four of which (except 345) map away from the active site of NA when projected onto the three-dimensional structure of avian influenza H5N1 NA, and substitutions of these residues adversely affected the NA-mediated viral particle release, suggesting that these residues are critical for NA enzymatic activity. CONCLUSION: Through extensive chimeric and mutational analyses, we have identified several residues, which map away from the active site and are critical for NA function. These findings provide new insights into NA-mediated pseudoviral particle release and may have important implications in drug design and therapeutics against influenza infection.

Funding

The laboratory research was supported by National Institutes of Health grant AI 059570 (to L. R.).

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Publisher Statement

The original source is available through BioMed Central at DOI: 10.1186/1743-422X-8-14. © 2011 Tisoncik et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher

BioMed Central

Language

en_US

issn

1743-422X

Issue date

13/01/2011

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