Premium
Regulation of arginase II by interferon regulatory factor 3 and the involvement of polyamines in the antiviral response
Author(s) -
Grandvaux Nathalie,
Gaboriau François,
Harris Jennifer,
tenOever Benjamin R.,
Lin Rongtuan,
Hiscott John
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04726.x
Subject(s) - sendai virus , jurkat cells , interferon , biology , irf1 , polyamine , interferon regulatory factors , transcription factor , vesicular stomatitis virus , virus , interferon stimulated gene , spermine , microbiology and biotechnology , innate immune system , gene , virology , immune system , biochemistry , enzyme , immunology , t cell
The innate antiviral response requires the induction of genes and proteins with activities that limit virus replication. Among these, the well‐characterized interferon β ( IFNB ) gene is regulated through the cooperation of AP‐1, NF‐κB and interferon regulatory factor 3 (IRF‐3) transcription factors. Using a constitutively active form of IRF‐3, IRF‐3 5D, we showed previously that IRF‐3 also regulates an IFN‐independent antiviral response through the direct induction of IFN‐stimulated genes. In this study, we report that the arginase II gene ( ArgII ) as well as ArgII protein concentrations and enzymatic activity are induced in IRF‐3 5D‐expressing and Sendai virus‐infected Jurkat cells in an IFN‐independent manner. ArgII is a critical enzyme in the polyamine‐biosynthetic pathway. Of the natural polyamines, spermine possesses antiviral activity and mediates apoptosis at physiological concentrations. Measurement of intracellular polyamine content revealed that expression of IRF‐3 5D induces polyamine production, but that Sendai virus and vesicular stomatitis virus infections do not. These results show for the first time that the ArgII gene is an early IRF‐3‐regulated gene, which participates in the IFN‐independent antiviral response through polyamine production and induction of apoptosis.