{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:56:55Z","timestamp":1790474215381,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010843","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1145613"],"award-info":[{"award-number":["APP1145613"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1123319"],"award-info":[{"award-number":["APP1123319"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFN\u025b) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs \u03b1, \u03b2 and \u03bb. We show the necessity of IFN\u025b for Zika Virus (ZIKV) protection by: increased susceptibility of IFN\u025b\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice; their \u201crescue\u201d by intravaginal recombinant IFN\u025b treatment and blockade of protective endogenous IFN\u025b by neutralising antibody. Complementary studies in human FRT cell lines showed IFN\u025b had potent anti-ZIKV activity, associated with transcriptome responses similar to IFN\u03bb but lacking the proinflammatory gene signature of IFN\u03b1. IFN\u025b activated STAT1\/2 pathways similar to IFN\u03b1 and \u03bb that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFN\u03b5 exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFN\u03b5. However, the IFN\u025b expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFN\u03b2 or \u03bb. Thus, the constitutive expression of IFN\u025b 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 IFN\u03b5 provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010843","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T13:38:50Z","timestamp":1678455530000},"page":"e1010843","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Rosa C.","family":"Coldbeck-Shackley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rosli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden J.","family":"Gearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodee A.","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"San S.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie H.","family":"Van der Hoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas 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