Effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease P.
The polymerase (PB2) and nucleocapsid (NP) genes encoded by the genome of influenza virus are essential for replication of the virus. When synthetic genes that express RNAs for external guide sequences targeted to the mRNAs of the PB2 and NP genes are stably incorporated into mouse cells in tissue culture, infection of these cells with influenza virus is nonproductive. Endogenous RNase P cleaves the targeted influenza virus mRNAs when they are in a complex with the external guide sequences. Targeting two different mRNAs simultaneously inhibits viral particle production more efficiently than does targeting only one mRNA.
Plehn-Dujowich
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Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Altman
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004722:Endoribonucleases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009975:Orthomyxoviridae / Q000502:physiology*; D016337:RNA, Catalytic / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase; D043262:Ribonuclease P; D014758:Viral Core Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D058727:RNA, Small Untranslated
D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C057027:PB2 protein, Influenzavirus A; D016337:RNA, Catalytic; D012333:RNA, Messenger; D014758:Viral Core Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase; D004722:Endoribonucleases; D043262:Ribonuclease P; D058727:RNA, Small Untranslated