4: Characterization of a novel interferon stimulated gene with antiviral activity
Interferon inducible genes are critical for the initiation of an effective antiviral response and for the clearance of virus from infected cells. These proteins exert their influence on viral replication via a myriad of different mechanisms, potentially influencing every step in the pathogens replicative cycle. Interferon stimulated genes have also been shown to mediate a wide array of cellular processes, including modulation of the immune response, cellular death and proliferation. Several hundred genes have been shown to be upregulated in response to interferon stimulation, however, only a fraction of these genes have been characterized to date. FLJ11286 (FLJ) is 291 aa in length, contains conserved cysteine residues and has homologues across the vertebrate taxon. We show that FLJ is upregulated in response to stimulation with type-I, II and III interferons in both a time and dose-dependent manner, and that disruption of interferon signaling through siRNA mediated knockdown of Interferon regulatory factor 9 results in decreased induction of FLJ after interferon treatment. Furthermore, we demonstrate that siRNA mediated knockdown of FLJ results in increased sensitivity of A549 cells to infection with Encephalomyocarditis virus. Overexpression of FLJ results in a corresponding decrease in viral titers. Here we demonstrate for the first time that FLJ is an interferon-stimulated gene with antiviral activity.