title: Adenovirus-mediated artificial MicroRNAs targeting matrix or nucleoprotein genes protect mice against lethal influenza virus challenge.
abstract: Influenza virus (IV) infection is a major public health problem, causing millions of cases of severe illness and as many as 500 000 deaths each year worldwide. Given the limitations of current prevention or treatment of acute influenza, novel therapies are needed. RNA interference (RNAi) through microRNAs (miRNA) is an emerging technology that can suppress virus replication in vitro and in vivo. Here, we describe a novel strategy for the treatment of infuenza based on RNAi delivered by a replication-defective adenovirus (Ad) vector, derived from chimpanzee serotype 68 (AdC68). Our results showed that artificial miRNAs (amiRNAs) specifically targeting conserved regions of the IV genome could effectively inhibit virus replication in human embryonic kidney 293 cells. Moreover, our results demonstrated that prophylactic treatment with AdC68 expressing amiRNAs directed against M1, M2 or nucleoprotein genes of IV completely protected mice from homologous A/PR8 virus challenge and partially protected the mice from heterologous influenza A virus strains such as H9N2 and H5N1. Collectively, our data demonstrate that amiRNAs targeting the conserved regions of influenza A virus delivered by Ad vectors should be pursued as a novel strategy for prophylaxis of IV infection in humans and animals.
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.affiliation: Shanghai Public Health Clinical Center, the Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Wistar Institute, Philadelphia, PA, USA.
authors.forename: H C J
authors.initials: HC
authors.lastname: Ertl
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D053127:Influenza A Virus, H9N2 Subtype / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology / Q000378:metabolism*; D015530:Nuclear Matrix / Q000235:genetics / Q000378:metabolism*; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D009698:Nucleoproteins
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