ADENOSINE DEAMINASE ACTING ON RNA 1 (ADAR1) SUPPRESSES THE INDUCTION OF INTERFERON BY MEASLES VIRUS.

Tuesday, 3rd of September 2013 Print
[source]Journal of Virology [|source]

This report  tests whether ADAR1 plays a role in virus-induced IFN-β expression using MV and whether any of the observed ADAR1-dependent responses were modulated by the viral V or C accessory protein. The study reports that IFN-β RNA expression was increased 100-fold or more following virus infection that, when cells stably deficient in ADAR1 were used. The anticipation that if PKR activation is central to the amplification of IFN-β RNA expression and if ADAR1 deficiency leads to increased virus-induced activation of PKR, then ADAR1 deficiency might result in increased expression of IFN-β transcripts was also observed. More interesting findings are available at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302501/

 

Abstract

ADAR1, the interferon (IFN)-inducible adenosine deaminase acting on RNA, catalyzes the C-6 deamination of adenosine (A) to produce inosine (I) in RNA substrates with a double-stranded character. Because double-stranded RNA is a known inducer of IFN, we tested the role of ADAR1 in IFN induction following virus infection. HeLa cells made stably deficient in ADAR1 (ADAR1kd) were compared to vector control (CONkd) and protein kinase PKR-deficient (PKRkd) cells for IFN-β induction following infection with either parental (wild-type [WT]) recombinant Moraten vaccine strain measles virus (MV) or isogenic knockout mutants deficient for either V (Vko) or C (Cko) protein expression. We observed potent IFN-β transcript induction in ADAR1kd cells by all three viruses; in contrast, in ADAR1-sufficient CONkd cells, only the Cko mutant virus was an effective inducer and the IFN-β RNA induction was amplified by PKR. The enhanced IFN-β transcript-inducing capacity of the WT and Vko viruses seen in ADAR1-deficient cells correlated with the enhanced activation of PKR, IFN regulatory factor IRF3, and activator of transcription ATF2, reaching levels similar to those seen in Ckovirus-infected cells. However, the level of IFN-β protein produced was not proportional to the level of IFN-β RNA but rather correlated inversely with the level of activated PKR. These results suggest that ADAR1 functions as an important suppressor of MV-mediated responses, including the activation of PKR and IRF3 and the induction of IFN-β RNA. Our findings further implicate a balanced interplay between PKR and ADAR1 in modulating IFN-β protein production following virus infection.

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