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Here we show that treatment of primary human vaginal and cervical epithelial cells with\u00a0interferon (IFN)-\u03b1\/\u03b2 or IFN-\u03bb induces host defense transcriptional signatures and inhibits ZIKV infection. We also assess the effects of IFNs on intravaginal infection of the FRT using ovariectomized mice treated with reproductive hormones. We find that mice receiving estradiol are protected against intravaginal ZIKV infection, independently of IFN-\u03b1\/\u03b2 or IFN-\u03bb signaling. In contrast, mice lacking IFN-\u03bb signaling sustain greater FRT infection when progesterone is administered. Exogenous IFN-\u03bb treatment confers an antiviral effect when mice receive both estradiol and progesterone, but not progesterone alone. Our results identify a hormonal stage-dependent role for IFN-\u03bb in controlling ZIKV infection in the FRT and suggest a path for minimizing sexual transmission of ZIKV in women.<\/jats:p>","DOI":"10.1038\/s41467-018-07993-2","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T13:28:50Z","timestamp":1547213330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Interferon lambda protects the female reproductive tract against Zika virus infection"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-7330","authenticated-orcid":false,"given":"Elizabeth A.","family":"Caine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Scheaffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Arora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-0886","authenticated-orcid":false,"given":"Konstantin","family":"Zaitsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim N.","family":"Artyomov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-6309","authenticated-orcid":false,"given":"Carolyn B.","family":"Coyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelle H.","family":"Moley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-3165","authenticated-orcid":false,"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,17]]},"reference":[{"key":"7993_CR1","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/nature20556","volume":"540","author":"J Govero","year":"2016","unstructured":"Govero, J. et al. 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