Open AccessInduction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript
Author(s) -
Petra Švančarová,
D Svetlíková,
Tatiana Betáková
Publication year - 2015
Publication title -
acta virologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 33
eISSN - 1336-2305
pISSN - 0001-723X
DOI - 10.4149/av_2015_02_148
Subject(s) - interferon , small hairpin rna , biology , rna interference , virology , transfection , small interfering rna , gene silencing , virus , microbiology and biotechnology , titer , influenza a virus , messenger rna , viral replication , rna , gene expression , gene , genetics
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.