Characterization, functional and signaling elucidation of pigeon (Columba livia) interferon-α: Knockdown p53 negatively modulates antiviral response. (January 2019)

• Record Type: Journal Article
• Authors: Li, Siwen; Wang, Yu; Zhao, Hongjing; Shao, Yizhi; Liu, Juanjuan; Xing, Mingwei
• Is Part Of: Developmental and comparative immunology. Volume 90(2019)
• Page Start: 29
• Page End: 40
• Publication Date: 2019-01
• Subjects: Columba livia interferon-α -- Antiviral activity -- p53 -- Autophagy -- Apoptosis -- Mdm2; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2018.08.017
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: The regulation of interferon-α signaling pathways is essential to protect the host from infection with a broad range of viruses. However, information regarding antiviral response and the specific molecular mechanism of Columba livia interferon-α (CoIFN-α) has not been reported to date. In this study, we cloned a 723bp complete ORF of CoIFN-α gene. The specific antiviral activity of CoIFN-α in VSV (TCID50 = 10 −5.87 /100 μL)-infected CEFs reached 5.5 × 10 5 U/mg. Moreover, our result indicated that the anti-VSV efficient of CoIFN-α might depend on the expression of NF-κB. CoIFN-α also showed high sensitivity to trypsin and relatively stable after acid, alkali or heat treatment. Moreover, CoIFN-α activated STAT/Jak signaling and autophagy to inhibit VSV-induced apoptosis. Although the expression of p53 was further increased, apoptosis was not involved in CoIFN-α against VSV. Notably, although STAT signaling was efficiently activated, knockdown p53 did inhibit the antiviral activity of the CoIFN-α via decreasing the expression of Mx1 but not weakened Jak phosphorylation. Moreover, VSV aggravated the apoptosis and the expression of cleaved Mdm2 in knockdown p53 under preincubated CoIFN-α. Taken together, p53 might as a highly interconnected regulator in IFN-α antiviral response and cleaved Mdm2 might as a dominant-negative regulator by competing with full length Mdm2 for p53 binding in virus infection. Overall, our research not only enriches CoIFN-α antiviral features but also helps explain that p53 enhance the CoIFN-α antiviral response against pigeon viral diseases. Highlights: The characterization and biological activity of Columba livia IFN-α were analyzed. Columba livia IFN-α project protective effects on virus-induced apoptosis. NF-κB is involved in the antiviral activity between CoIFN-α and ChIFN-α resisted VSV. Knockdown p53 decrease the expression of Mx1 but not weakened Jak2 phosphorylation. Cleaved Mdm2 might enhances the induction of p53 for innate cellular immunity.