Interferon regulatory factor 3-CL, an isoform of IRF3, antagonizes activity of IRF3.

Interferon regulatory factor 3 (IRF3), one member of the IRF family, plays a central role in induction of type I interferon (IFN) and regulation of apoptosis. Controlled activity of IRF3 is essential for its functions. During reverse transcription (RT)-PCR to clone the full-length open reading frame (ORF) of IRF3, we cloned a full-length ORF encoding an isoform of IRF3, termed as IRF3-CL, and has a unique carboxyl-terminus of 125 amino acids. IRF3-CL is ubiquitously expressed in distinct cell lines. Overexpression of IRF3-CL inhibits Sendai virus (SeV)-triggered induction of IFN-β and SeV-induced and inhibitor of NF-κB kinase-ε (IKKε)-mediated nuclear translocation of IRF3. When IKKε is overexpressed, IRF3-CL is associated with IRF3. These results suggest that IRF3-CL, the alternative splicing isoform of IRF-3, may function as a negative regulator of IRF3.