MicroRNA-mediated species-specific attenuation of influenza A virus

被引：121

作者：

Perez, Jasmine T. ^{[1
]}

Pham, Alissa M. ^{[1
]}

Lorini, Maria H. ^{[2
]}

Chua, Mark A. ^{[3
]}

Steel, John ^{[2
]}

tenOever, Benjamin R. ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Sch Med, Microbiol Grad Sch Training Program, New York, NY USA

[2] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA

[3] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY USA

来源：

NATURE BIOTECHNOLOGY | 2009年 / 27卷 / 06期

基金：

美国国家卫生研究院;

关键词：

NS1; PROTEIN; SMALL RNA; EXPRESSION; REPLICATION; IMMUNITY; RESCUE; SYSTEM;

D O I：

10.1038/nbt.1542

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：572 / U117

页数：7

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