title: Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs.
abstract: IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals--up to 10% of Asians, 50% of Europeans, and 90% of Africans--carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable-they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors: Ashley
authors: A
authors: Paquin
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors: Olusegun O
authors: OO
authors: Onabajo
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors: Wei
authors: W
authors: Tang
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
authors: Ludmila
authors: L
authors: Prokunina-Olsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008156:Luciferases / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection; D000095022:Interferon Lambda
chemical_list: D007378:Interleukins; D008156:Luciferases; D011994:Recombinant Proteins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda