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Here, we show a neutralizing antibody response, dependent on CD4<jats:sup>+<\/jats:sup> T cells and IFN\u03b3 signaling, which we detected during the first week of infection and is associated with reduced viral load in the brain, prevention of rapid disease onset and survival. We demonstrate participation of these components in the resistance to ZIKV during primary infection and in murine adoptive transfer models of heterologous ZIKV infection in a background of IFNR deficiency. The protective effect of adoptively transferred CD4<jats:sup>+<\/jats:sup> T cells requires IFN\u03b3 signaling, CD8<jats:sup>+<\/jats:sup> T cells and B lymphocytes in recipient mice. Together, this indicates the importance of CD4<jats:sup>+<\/jats:sup> T cell responses in future vaccine design for ZIKV.<\/jats:p>","DOI":"10.1038\/s41467-018-05519-4","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T13:33:54Z","timestamp":1533130434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Critical role of CD4+ T cells and IFN\u03b3 signaling in antibody-mediated resistance to Zika virus infection"],"prefix":"10.1038","volume":"9","author":[{"given":"Carolina G. 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