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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Perez JT,Pham AM,Lorini MH,Chua MA,Steel J,tenOever BR

doi

10.1038/nbt.1542

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

572-6

issue

6

eissn

1087-0156

issn

1546-1696

pii

nbt.1542

journal_volume

27

pub_type

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