Comparative Functional Analysis of 12 Mammalian IFN-?4 Orthologs

Paquin, Ashley; Onabajo, Olusegun O.; Tang, Wei; Prokunina-Olsson, Ludmila

IFN-l4 is a novel type-III IFN with moderate similarity to other type-III IFNs; it has 29% amino acid identity with IFN-l3, the most related member of this family (Prokunina-Olsson and others 2013). The three other type-III IFNs (IFN-l1, IFN-l2, and IFN-l3), which share high protein identity (81% between IFN-l1 and IFN-l2 and 96% between IFN-l2 and IFN-l3), were discovered in 2003 (Kotenko and others 2003; Sheppard and others 2003) . All four type-III IFNs are encoded by a 55 Kb genomic cluster on the human chromosome19q13.2. Due to low sequence similarity between IFNL4 and the genes for other type-III IFNs, IFNL4 could not be identified by a homology search. The reference human genome sequence has the rs368234815-TT allele, which does not support the IFN-l4 ORF, thus the existence of IFN-l4 was not predicted. IFN-l4 was identified by direct cloning and annotation of sequences discovered through RNA sequencing of human hepatocytes treated with PolyI:C to mimic viral infection (Prokunina-Olsson and others 2013).