@article{853054481cb5454eac6cef2cc0b400ba,
title = "MicroRNA-mediated species-specific attenuation of influenza A virus",
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.",
author = "Perez, {Jasmine T.} and Pham, {Alissa M.} and Lorini, {Maria H.} and Chua, {Mark A.} and John Steel and Tenoever, {Benjamin R.}",
note = "Funding Information: This material is based upon work supported in part by the US Army Research Laboratory and the US Army Research Office under grant number 54677-LS-YIP. J.T.P. is supported by the NYU-MSSM Mechanisms of Virus-Host Interactions National Institutes of Health T32 training grant (no. AI007647-09). B.R.t. is supported in part by the Pew Charitable Funds. We thank A. Garcia-Sastre for giving us polyclonal A/PR/8/34 (MSSM, NY); G. Sen for ISG54 (Cleveland Clinic, OH, USA); A. Fernandez-Sesma (MSSM, NY) for primary human dendritic cell RNA; A. Tarakhovsky (Rockefeller University, NY) and D. O{\textquoteright}Carroll (EMBL, Monterotondo, Italy) for Dicer−/− murine fibroblasts; E. Makeyev (Nanyang Technological University, Singapore) for firefly luciferase constructs containing miR-124 MREs and control SV40 3¢ UTRs; and P. Palese (MSSM, NY) for pPol-I driven nucleoprotein vector, monoclonal nucleoprotein and A/PR/8/34 NS1. We thank members of the Palese and Garcia-Sastre labs for advice, reagents and comments during the course of this work.",
year = "2009",
month = jun,
doi = "10.1038/nbt.1542",
language = "English",
volume = "27",
pages = "572--576",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "6",
}