Although one study in mice suggested an estrous cycle-dependent protective role of IFN-ε against infections in the vagina26, in our model, estradiol treatment conferred protection against intravaginal ZIKV infection in mice with acquired or genetic deficiencies in type I IFN signaling, suggesting that IFN-ε was not the dominant antiviral cytokine during the estrous phase. The gene discussed is IFNE; the disease is infection.