Characterization of the rock pigeon type IV interferon system reveals conserved tyrosine-based signaling via the IFN-υR1/IL10RB complex

Abstract

Abstract Type IV interferon (IFN), a recently identified class of IFN, exhibits broad-spectrum antiviral and antibacterial functions across species. In this study, the type IV IFN gene, IFN - υ , and its cognate receptor subunits (IFN-υR1 and IL10RB) were functionally characterized in an avian species, the rock pigeon ( Columba livia ). Phylogenetic analysis showed that rock pigeon IFN-υ, IFN-υR1, and IL10RB were clustered closely with their respective orthologs in other vertebrates. Expression profiling revealed the constitutive transcription of these genes across multiple tissues. Furthermore, the expression of these genes was significantly upregulated upon stimulation with the viral double-stranded RNA (dsRNA) mimic, poly(I:C). The recombinant rock pigeon IFN-υ activated the canonical Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling pathway, inducing STAT1 phosphorylation and the consequent expression of key interferon-stimulated genes (ISGs) such as OAS1 , PKR, and RSAD2 . Using overexpression and knockdown assays, the biological activity of IFN-υ was found to signal through a heterodimeric receptor complex comprising IFN-υR1 and IL10RB. Importantly, two conserved tyrosine residues (Tyr 334 and Tyr 525 ) within the intracellular domain of IFN-υR1 were found essential for IFN-υ-mediated JAK-STAT pathway activation, ISG induction, and antiviral activity. These findings elucidate the conserved functional architecture and signaling mechanism of type IV IFN in vertebrates.