title: Induction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript.
abstract: RNA interference (RNAi) represents a form of post-transcriptional gene silencing mediated by small interfering RNAs (siRNA) and provides a powerful tool to specifically inhibit viral infection. To investigate therapeutic capacity of siRNAs targeting M gene, six vectors with U1-short hairpin RNA (shRNA) expression system were prepared and tested in infected cells and animals. In infected cells, three of six shRNAs targeting M1 gene significantly (P <0,01) reduced the virus titer to 66%, 45% or 21%, respectively. Replication of IAV and levels of M1 RNAs were significantly reduced in the cells transfected with shRNAs, which decreased the virus titer. IFN-α/β altered in shRNAs-treated cells. The level of IFN-λ (type III interferon) mRNA was significantly increased in the infected cells treated with shM22, shM349, shM522, and (type I interferon) as well as IP-10 (type II interferon) mRNAs were not significantly their mixtures. The increased level of IFN-λ mRNA corresponded to significantly increased level of RIG-1 mRNA. shRNAs inhibited influenza virus infection in a gene-specific manner in co-operation with IFN-λ. Some constructs targeting the M1 transcript prolonged the survival of infected mice.
authors.forename: P
authors.initials: P
authors.lastname: Švančarová
authors.forename: D
authors.initials: D
authors.lastname: Svetlíková
authors.forename: T
authors.initials: T
authors.lastname: Betáková
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000378:metabolism; D007251:Influenza, Human / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D007378:Interleukins; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; C000594666:IL28A protein, mouse; D000095022:Interferon Lambda; C488936:M1 protein, Influenza A virus
keywords: influenza virus; shRNA; M1 protein.