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- Title
MicroRNA-mediated species-specific attenuation of influenza A virus.
- Authors
Perez, Jasmine T; Pham, Alissa M; Lorini, Maria H; Chua, Mark A; Steel, John; tenOever, Benjamin R
- Abstract
Influenza A virus leads to yearly epidemics and sporadic pandemics. Present prophylactic strategies focus on egg-grown, live, attenuated influenza vaccines (LAIVs), in which attenuation is generated by conferring temperature sensitivity onto the virus. Here we describe an alternative approach to attenuating influenza A virus based on microRNA-mediated gene silencing. By incorporating nonavian microRNA response elements (MREs) into the open-reading frame of the viral nucleoprotein, we generate reassortant LAIVs for H1N1 and H5N1 that are attenuated in mice but not in eggs. MRE-based LAIVs show a greater than two-log reduction in mortality compared with control viruses lacking MREs and elicit a diverse antibody response. This approach might be combined with existing LAIVs to increase attenuation and improve vaccine safety.
- Publication
Nature biotechnology, 2009, Vol 27, Issue 6, p572
- ISSN
1546-1696
- Publication type
Journal Article
- DOI
10.1038/nbt.1542