Abstract
No effective therapy or vaccine exists to protect against the next Zika virus (ZIKV) outbreak. ZIKV has been detected in multiple organs of infected people, including immune-privileged sites like the brain, eyes, and reproductive tract. ZIKV replication in the reproductive tract is of high concern; ZIKV can be transmitted sexually or to the developing fetus of pregnant women, resulting in severe congenital defects. Here, we show that ZIKV-infected immunocompetent mice rapidly controlled viremia with no viral rebound following T cell depletion. In contrast, mice genetically deficient in B and T cells (immunodeficient mice) supported sustained ZIKV replication in all tissues examined. Treatment of ZIKV-infected immunodeficient mice with the novel nucleoside analog 7-deaza-7-fluoro-2'-C-methyladenosine (DFMA) significantly reduced viremia and prolonged survival, validating immunodeficient mice for efficacy studies of ZIKV prevention and therapeutic approaches. Importantly, we demonstrate that treatment of ZIKV-infected animals with a dengue virus cross-neutralizing antibody (EDE1, C10) suppressed systemic ZIKV replication, including in the brain, eye, and male and female reproductive tracts.IMPORTANCESince 2007, Zika virus (ZIKV) infections have been documented in over 80 countries and territories, resulting in two major outbreaks thus far. ZIKV has been detected in multiple organs of infected people, including immune-privileged sites like the brain, eyes, and reproductive tract. ZIKV replication in the reproductive tract is of high concern as ZIKV can be transmitted sexually or to the developing fetus of pregnant women, resulting in severe congenital defects. Currently, no effective therapy or vaccine exists to protect against the next outbreak. Here, we developed a preclinical animal model for ZIKV infection that we used to evaluate the efficacy of a dengue virus cross-neutralizing antibody for prevention/treatment of ZIKV infection. The antibody suppressed virus replication in blood and tissues, including the reproductive tract, suggesting that passive administration of ZIKV neutralizing antibodies could be used during future ZIKV outbreaks in high-risk populations to prevent ZIKV transmission.