Abstract
Case reports of Zika virus (ZIKV) sexual transmission and genital persistence are mounting. Venereal transmission and genital persistence threaten public health within and beyond the range of ZIKV's mosquito vectors. In this study, we administered ZIKV into the vaginas of AG129 mice and LysMCre(+)IFNAR(fl/fl) C57BL/6 mice after hormonal treatments. Mice infected during estrus-like phase were resistant to vaginal infection. In contrast, when infected during diestrus-like phase, AG129 mice succumbed to infection, whereas LysMCre(+)IFNAR(fl/fl) mice experienced transient illness. Patency of transgenital transmission (TGT) in diestrus-like mice was demonstrated by detection of viremia and ZIKV replication in spleen and brain, and viral RNA persisted in vaginal washes as late as 10 days post-infection. In these lethal and sublethal mouse models, this study indicates that intravaginal deposition of ZIKV can cause TGT, hormonal changes in the female reproductive tract (FRT) influence transmission, and ZIKV replication persists in the FRT for several days.