دورية أكاديمية
أعرض في EDS

Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.

التفاصيل البيبلوغرافية
العنوان: Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.
المؤلفون: Coldbeck-Shackley RC; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia., Romeo O; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia., Rosli S; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Gearing LJ; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Gould JA; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Lim SS; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Van der Hoek KH; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia., Eyre NS; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia., Shue B; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia., Robertson SA; Robinson Research Institute, The University of Adelaide, South Australia, Australia., Best SM; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton Montana, United States of America., Tate MD; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Hertzog PJ; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia.; Department of Molecular and Translational Sciences, Monash University, Victoria, Australia., Beard MR; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, South Australia, Australia.
المصدر: PLoS pathogens [PLoS Pathog] 2023 Mar 10; Vol. 19 (3), pp. e1010843. Date of Electronic Publication: 2023 Mar 10 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Zika Virus*/genetics , Zika Virus Infection*, Animals ; Female ; Humans ; Mice ; Antiviral Agents/pharmacology ; Genitalia, Female ; Immunologic Factors ; Interferon-alpha/pharmacology
مستخلص: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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المشرفين على المادة: 0 (Antiviral Agents)
0 (Immunologic Factors)
0 (Interferon-alpha)
0 (IFNE protein, human)
تواريخ الأحداث: Date Created: 20230310 Date Completed: 20230331 Latest Revision: 20230409
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10032502
DOI: 10.1371/journal.ppat.1010843
PMID: 36897927
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1010843