title: Short peptide type I interferon mimetics: therapeutics for experimental allergic encephalomyelitis, melanoma, and viral infections.
abstract: The classical canonical model of interferon (IFN) signaling focuses solely on the activation of STAT transcription factors, which limits the model in terms of specific gene activation, associated epigenetic events, and IFN mimetic development. Accordingly, we have developed a noncanonical model of IFN signaling and report the development of short type I IFN peptide mimetic peptides based on the model. The mimetics, human IFNα1(152-189), human IFNβ(150-187), and ovine IFNτ(156-195) are derived from the C-terminus of the parent IFNs and function intracellularly based on the noncanonical model. Vaccinia virus produces a decoy IFN receptor (B18R) that inhibits type I IFN, but the IFN mimetics bypass B18R for effective antiviral activity. By contrast, both parent IFNs and mimetics inhibited vesicular stomatitis virus. The mimetics also possessed anti-tumor activity against murine melanoma B16 tumor cells in culture and in mice, including synergizing with suppressor of cytokine signaling 1 antagonist. Finally, the mimetics were potent therapeutics against experimental allergic encephalomyelitis, a mouse model of multiple sclerosis. The mimetics lack toxic side effects of the parent IFNs and, thus, are a potent therapeutic replacement of IFNs as therapeutics.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida , Gainesville, Florida.
authors.forename: Chulbul M
authors.initials: CM
authors.lastname: Ahmed
authors.forename: Howard M
authors.initials: HM
authors.lastname: Johnson
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000138:chemical synthesis / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D014777:Virus Diseases / Q000188:drug therapy*
chemical_list: D007370:Interferon Type I; D010446:Peptide Fragments