Abstract
Type-I interferons (IFNs) form a large family of cytokines that primarily act to control the early development of viral infections. Typical type-I IFN genes, such as those encoding IFN-α or IFN-β are upregulated by viral infection in many cell types. In contrast, the gene encoding IFN-ε was reported to be constitutively expressed by cells of the female reproductive tract and to contribute to the protection against vaginal infections with herpes simplex virus 2 and Chlamydia muridarum. Our data confirm the lack of induction of IFN-ε expression after viral infection and the constitutive expression of IFN-ε by cells of the female but also of the male reproductive organs. Interestingly, when expressed from transfected expression plasmids in 293T, HeLa or Neuro2A cells, the mouse and human IFN-ε precursors were inefficiently processed and secretion of IFN-ε was minimal. Analysis of chimeric constructs produced between IFN-ε and limitin (IFN-ζ) showed that both the signal peptide and the mature moiety of IFN-ε contribute to poor processing of the precursor. Immunofluorescent detection of FLAG-tagged IFN-ε in transfected cells suggested that IFN-ε and chimeric proteins were defective for progression through the secretory pathway. IFN-ε did not, however, act intracellularly and impart an antiviral state to producing cells. Given the constitutive expression of IFN-ε in specialized cells and the poor processing of IFN-ε precursor in fibroblasts and cell lines, we hypothesize that IFN-ε secretion may require a co-factor specifically expressed in cells of the reproductive organs, that might secure the system against aberrant release of this IFN.
Highlights
Type I interferons (IFNs), are a family of cytokines endowed with a potent antiviral activity [1]
Type I IFNs are reported to bind a common heterodimeric receptor (IFNAR) [2], thereby eliciting a signal transduction cascade leading to the transcriptional activation of hundreds of interferon stimulated genes (ISGs) that contribute to antiviral activity [3,4,5]
We show that maturation and secretion of IFN-ε is inefficient in cell lines and fibroblasts, and we hypothesize that IFN-ε secretion by cells of reproductive organs involves a specific co-factor lacking in other cells
Summary
Type I interferons (IFNs), are a family of cytokines endowed with a potent antiviral activity [1]. Members of this family referred to as IFN-α/β, include IFN-α, IFN-β, IFN-ε, IFN-κ, IFNω, IFN-τ (ovines and bovines) and IFN-ζ or limitin (mice). It has been shown that human IFN-ε can bind to the type I IFN receptor (IFNAR) [11] and possesses some antiviral activity [9,12,13]. We confirm the constitutive expression of IFN-ε by cells of the female and the male reproductive organs. We show that maturation and secretion of IFN-ε is inefficient in cell lines and fibroblasts, and we hypothesize that IFN-ε secretion by cells of reproductive organs involves a specific co-factor lacking in other cells
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