title: RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription.
abstract: Influenza A virus causes widespread infection in the human respiratory tract, but existing vaccines and drug therapy are of limited value. Here we show that short interfering RNAs (siRNAs) specific for conserved regions of the viral genome can potently inhibit influenza virus production in both cell lines and embryonated chicken eggs. The inhibition depends on the presence of a functional antisense strand in the siRNA duplex, suggesting that viral mRNA is the target of RNA interference. However, siRNA specific for nucleocapsid (NP) or a component of the RNA transcriptase (PA) abolished the accumulation of not only the corresponding mRNA but also virion RNA and its complementary RNA. These siRNAs also broadly inhibited the accumulation of other viral, but not cellular, RNAs. The findings reveal that newly synthesized NP and PA proteins are required for influenza virus transcription and replication and provide a basis for the development of siRNAs as prophylaxis and therapy for influenza infection in humans.
authors.affiliation: Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ge
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.forename: Tam
authors.initials: T
authors.lastname: Nguyen
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Shen
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
authors.forename: Herman N
authors.initials: HN
authors.lastname: Eisen
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology*; D019590:Nucleocapsid Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D018075:RNA, Complementary / Q000378:metabolism; D012330:RNA, Double-Stranded; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
chemical_list: D019590:Nucleocapsid Proteins; D018075:RNA, Complementary; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D012313:RNA