Evaluation of the antiviral effect of exogenous human IFN-lambda mRNA against influenza virus in vitro

Abstract

Objective: Despite the fact that exogenous mRNA has great prospects for the development of therapeutic medicine, its use is still limited. As the immediate protein precursor, positive-stranded mRNA may represent a suitable alternative to prevent of viral infections. Results: Here, we focused our efforts on making the exogenous RNA encoding human interferon lambda (hIFN-λ1). Using the in vitro transcription method, we obtained hIFN-λ1 RNA and showed that it is capable to rapid translation in transfected cells. We compared the translation efficiency of mRNAs containing unmodified and modified (pseudouridine and 5-methyl-cytidine) nucleosides. Our results showed that the level of hIFN-λ1 during translation from containing modified nucleosides mRNA was 10-fold or more times higher compare to unmodified mRNA. We found that the delivery of exogenous mRNA encoding GFP and hIFN-λ1 in cells resulted in an increase of MDA5, MxA, OAS-1, and IFN-αexpression, which indicate to the activation of innate immune response. At last it was shown that mRNA encoding hIFN-λ1 significantly reduced the reproduction of A/California/07/09 (H1N1pdm09) in comparison with the nonspecific mRNA encoding GFP.