ArticlePLoS pathogens2023
Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- IFN-κ directs antiviral immunity in human skin.bioRxiv : the preprint server for biology · 2026Article
- Age-dependent expression and antiviral activity of interferon epsilon in respiratory epithelium.Journal of virology · 2026Article
- Article
- Innate immune responses to pathogens at the maternal-fetal interface.Nature reviews. Immunology · 2025Review
- Exploring the vaginal ecosystem: insights into host-microbe interactions and microbial community dynamics.Infection and immunity · 2025Review
- Article
- The first trimester human placenta responds to Zika virus infection inducing an interferon (IFN) and antiviral interferon stimulated gene (ISG) response.Virology journal · 2025Article
- Interferon Epsilon: Properties and Functions.Current molecular medicine · 2025Review
- Interferon epsilon is produced in the testis and protects the male reproductive tract against virus infection, inflammation and damage.PLoS pathogens · 2024Article
- Interferon Epsilon-Mediated Antiviral Activity Against Human Metapneumovirus and Respiratory Syncytial Virus.Vaccines · 2024Article
- Article
- Article
- Functional interferon-epsilon gene polymorphisms and sexually transmitted infections of the endometrium.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ-/- mice; their "rescue" by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.
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