Human Consensus Interferons: Bridging the Natural and Artificial Cytokines with Intrinsic Disorder

Document Type

Article

Publication Date

2015

Keywords

cIFNconsensus interferon, consensus interferon, EDHSEgyptian Demographic Health Survey, Egyptian Demographic Health Survey, FDAFood and Drug Administration, Food and Drug Administration, HBVhepatitis B virus, hepatitis B virus, HCVhepatitis C virus, hepatitis C virus, IFNinterferon, interferon, IFNARIFN-α/β receptor, IFN-α/β receptor, IFNGRIFN-γ receptor, IFN-γ receptor, IRF9IFN-regulatory factor 9, IFN-regulatory factor 9, ISGIFN-stimulated gene, IFN-stimulated gene, ISGF3ISG factor 3, ISG factor 3, ISREIFN-stimulated response element, IFN-stimulated response element, JAKJanus activated kinase, Janus activated kinase, PCRpolymerase chain reaction, polymerase chain reaction, PTMposttranslational modification, posttranslational modification, STRINGSearch Tool for the Retrieval of Interacting Genes, Search Tool for the Retrieval of Interacting Genes, TYK2tyrosine kinase 2, tyrosine kinase 2, Consensus interferon, Interferon, Protein intrinsic disorder, Artificial protein, Hepatitis C virus

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.cytogfr.2015.07.012

Abstract

The consensus interferons are artificially engineered proteins that combine most of the therapeutic features of natural human α-interferons and show high anti-cancer and anti-viral activities. Egyptian patients infected with hepatitis C virus (HCV) genotype 4 show lower responses to interferon (IFN) therapy than the distributed worldwide patients infected with the other HCV genotypes. Numerous studies have reported that patients with hepatitis C who have not responded to a previous standard IFN-alpha therapy or those who relapsed following treatment cessation may benefit from retreatment with consensus IFN-α (cIFN-α). IFNs-α are shown here to have functionally important disordered regions. Furthermore, a strong correlation is established between the peculiarities of disorder profiles of these proteins and their known structural features. Intrinsic disorder profiles of existing cIFNs-α possess remarkable similarity to the consensus disorder profile calculated as averaged disorder predispositions of all human IFNs-α. If the peculiarities of disorder distribution within the protein sequence are related to protein functionality, then comparison of the disorder profiles of artificial cIFNs (query profiles) with the averaged disorder predisposition profile of human IFNs-α (target profile) can be used in the design of novel cIFNs. The goal here would be to achieve a close similarity between the query and target profiles by manipulating the cIFN sequence.

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Yes

Citation / Publisher Attribution

Cytokine & Growth Factor Reviews, v. 26, issue 6, p. 637-645

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