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.
authors.affiliation: Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Jasmine T
authors.initials: JT
authors.lastname: Perez
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Pham
authors.forename: Maria H
authors.initials: MH
authors.lastname: Lorini
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chua
authors.forename: John
authors.initials: J
authors.lastname: Steel
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: tenOever
mesh_terms: D000818:Animals; D001835:Body Weight; D002460:Cell Line; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D013045:Species Specificity; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D035683:MicroRNAs; D012367:RNA, Viral; D014613:Vaccines, Attenuated