MicroRNA-mediated species-specific attenuation of influenza A virus.
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.
Perez
Jasmine T
JT
Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, New York, USA.
Pham
Alissa M
AM
Lorini
Maria H
MH
Chua
Mark A
MA
Steel
John
J
tenOever
Benjamin R
BR
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
D007252:Influenza Vaccines; D035683:MicroRNAs; D012367:RNA, Viral; D014613:Vaccines, Attenuated