الفهرس 
cvover englishOnly 14 pages are availabe for public view
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Abstract
In the present study, we proven that peroxisomes, mitochondria and endoplasmic reticulum are important sites of antiviral signal transduction. Recent studies implicate the interferon regulatory factors (IRF), IRF-7, as key activators of Type 1 interferon genes. IRF-7 is regulated in part by virus induced C-terminal phosphorylation, leading to nuclear translocation, stimulation of DNA binding, and transcriptional activities. Using tagged versions of IRF-7-Flag and IRF-7-V5, the formation of homodimers was detected by co-immunoprecipitation. These results demonstrate that IRF-7 transcription factors possess distinct structural characteristics that impart complementary rather than redundant functional roles in cytokine gene activation. Here in the present study, we have genetically characterized chicken IFIT and revealed that chickens, in contrast to other vertebrates, encode only one IFIT gene (chIFIT5). The chIFIT5 gene was transcriptionally highly responsive to both type I IFNs and RNA viruses (IAV and NDV) and interestingly this responsiveness was mapped to ISRE motif in the cis-acting elements. We also demonstrated that chIFIT5 specifically interacts with ssRNA carrying 5′-ppp moiety. Through this interaction, chIFIT5 applies strong antiviral activities in lentivirus-transduced stable cell lines whereas CRISPR/Cas9-mediated chIFIT5 knockout promoted virus replication. Finally, employing the RCAS-based retroviral gene transfer vector system, we generated transgenic chicken embryos expressing chIFIT5 and demonstrated its antiviral potential in ovo. These findings propose the potential of innate immune genes in conferring genetic resistance in chickens against highly pathogenic and zoonotic viral pathogens causing sever disease in both animals and humans.