Letter abstract
Nature Biotechnology 27, 572 - 576 (2009)
Published online: 31 May 2009 | doi:10.1038/nbt.1542
MicroRNA-mediated species-specific attenuation of influenza A virus
Jasmine T Perez1, Alissa M Pham1, Maria H Lorini2, Mark A Chua3, John Steel2 & Benjamin R tenOever1,2,3
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.
- Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, New York, USA.
- Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
- Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York, USA.
Correspondence to: Benjamin R tenOever1,2,3 e-mail: benjamin.tenoever@mssm.edu
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