Upon infection with many RNA viruses, the cytoplasmic retinoic acid inducible gene‐I (RIG‐I) pathway activates the latent transcription factor IRF‐3, causing its nuclear translocation and the induction of many antiviral genes, including those encoding interferons. Here, we report a novel and distinct activity of IRF‐3, in virus‐infected cells, that induces apoptosis. Using genetically defective mouse and human cell lines, we demonstrated that, although both pathways required the presence of RIG‐I, IPS1, TRAF3 and TBK1, only the apoptotic pathway required the presence of TRAF2 and TRAF6 in addition. More importantly, transcriptionally inactive IRF‐3 mutants, such as the one missing its DNA‐binding domain, could efficiently mediate apoptosis. Apoptosis was triggered by the direct interaction of IRF‐3, through a newly identified BH3 domain, with the pro‐apoptotic protein Bax, their co‐translocation to the mitochondria and the resulting activation of the mitochondrial apoptotic pathway. Thus, IRF‐3 is a dual‐action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell. There is a [Have you seen ...?][1] (May 2010) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2010.79

We describe a vaccinialike virus, Araçatuba virus, associated with a cowpoxlike outbreak in a dairy herd and a related case of human infection. Diagnosis was based on virus growth characteristics, electron microscopy, and molecular biology techniques. Molecular characterization of the virus was done by using polymerase chain reaction amplification, cloning, and DNA sequencing of conserved orthopoxvirus genes such as the vaccinia growth factor (VGF), thymidine kinase (TK), and hemagglutinin. We used VGF-homologous and TK gene nucleotide sequences to construct a phylogenetic tree for comparison with other poxviruses. Gene sequences showed 99% homology with vaccinia virus genes and were clustered together with the isolated virus in the phylogenetic tree. Araçatuba virus is very similar to Cantagalo virus, showing the same signature deletion in the gene. Araçatuba virus could be a novel vaccinialike virus or could represent the spread of Cantagalo virus.