Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ

Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1074/jbc.M117.800755
Journal or Publication Title: Journal of Biological Chemistry
Volume: 293
Number: 9
Page Range: pp. 3168-3179
Date: 2017
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1074/jbc.M117.800755
ISSN: 0021-9258
Date Deposited: 03 Jan 2021 22:37
Abstract:

The type I interferons (IFNs) are a family of cytokines with diverse biological activities, including antiviral, antiproliferative, and immunoregulatory functions. The discovery of the hormonally regulated, constitutively expressed IFNϵ has suggested a function for IFNs in reproductive tract homeostasis and protection from infections, but its intrinsic activities are untested. We report here the expression, purification, and functional characterization of murine IFNϵ (mIFNϵ). Recombinant mIFNϵ (rmIFNϵ) exhibited an α-helical fold characteristic of type I IFNs and bound to IFNα/β receptor 1 (IFNAR1) and IFNAR2, but, unusually, it had a preference for IFNAR1. Nevertheless, rmIFNϵ induced typical type I IFN signaling activity, including STAT1 phosphorylation and activation of canonical type I IFN signaling reporters, demonstrating that it uses the JAK-STAT signaling pathway. We also found that rmIFNϵ induces the activation of T, B, and NK cells and exhibits antiviral, antiproliferative, and antibacterial activities typical of type I IFNs, albeit with 100-1000-fold reduced potency compared with rmIFNα1 and rmIFNβ. Surprisingly, although the type I IFNs generally do not display cross-species activities, rmIFNϵ exhibited high antiviral activity on human cells, suppressing HIV replication and inducing the expression of known HIV restriction factors in human lymphocytes. Our findings define the intrinsic properties of murine IFNϵ, indicating that it distinctly interacts with IFNAR and elicits pathogen-suppressing activity with a potency enabling host defense but with limited toxicity, appropriate for a protein expressed constitutively in a sensitive mucosal site, such as the reproductive tract.

Keywords: immunology; innate immunity; interferon; protein expression; signal transduction.

© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Creators:
Creators
Email
Stifter, Sebastian A.
UNSPECIFIED
Matthews, Antony Y.
UNSPECIFIED
Mangan, Niamh E.
UNSPECIFIED
Fung, Ka Yee
UNSPECIFIED
Drew, Alexander
UNSPECIFIED
Tate, Michelle D.
UNSPECIFIED
Soares da Costa, Tatiana P.
UNSPECIFIED
Hampsey, Daniel
UNSPECIFIED
Mayall, Jemma
UNSPECIFIED
Hansbro, Phil M.
UNSPECIFIED
Garcia Minambres, Albert
UNSPECIFIED
Eid, Sahar G.
UNSPECIFIED
Mak, Johnson
UNSPECIFIED
Scoble, Judy
UNSPECIFIED
Lovrecz, George
UNSPECIFIED
deWeerd, Nicole A.
UNSPECIFIED
Hertzog, Paul J.
UNSPECIFIED
Last Modified: 03 Jan 2021 22:37
URI: https://eprints.centenary.org.au/id/eprint/537

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