title: Albumin fusion of interleukin-28B: production and characterization of its biological activities and protein stability.
abstract: The cytokine interleukin-28B (IL-28B) has potential antiviral properties and regulatory roles in adaptive cellular immunity. A genome-wide association study identified a single nucleotide polymorphism near the IL-28B gene that strongly predicts response to hepatitis C treatment with interferon and ribavirin. In this study, we produced human serum albumin (HSA) fused to interleukin-28B (HSA-IL28B) in an attempt to determine the effects of albumin fusion on anti-Hepatitis C virus (HCV) activity and protein stability. HSA-IL28B was expressed at high levels in the yeast expression system we used and was easily purified. The biological activities of IL-28B were only retained when HSA was fused at the N-terminus. Compared with the native IL-28B, HSA-IL28B showed improved protein stability. HSA-IL28B inhibited HCV infection through the membrane receptors IL28R1 and IL10R2. Additionally, we demonstrated that HSA-IL28B was able to induce interferon-stimulated genes, phosphorylate intracellular STAT1, and act in restricted cell types. Our findings highlight the potential clinical applications of the fusion protein during virus infection and for immune regulation.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Youhui
authors.initials: Y
authors.lastname: Si
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Niu
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Xiuying
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D022781:Hepatocytes / Q000187:drug effects* / Q000821:virology; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D012709:Serum Albumin / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D007372:Interferons; D007378:Interleukins; D008156:Luciferases; D020033:Protein Isoforms; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D012709:Serum Albumin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494079:STAT1 protein, human