Adults contracting Zika virus (ZIKV) exhibit mild cold-like symptoms, whereas newborn babiesexhibit fetal defects ranging from mild growth retardation to miscarriage. Aside from transmission via mosquito, ZIKV is also sexually transmitted, which introduces the possibility that ZIKV infection could occur shortly after conception. However, the mechanisms underlying ZIKV-induced birth defects in early development are not understood. I hypothesize that sexually transmitted ZIKA virus infects... Show moreAdults contracting Zika virus (ZIKV) exhibit mild cold-like symptoms, whereas newborn babiesexhibit fetal defects ranging from mild growth retardation to miscarriage. Aside from transmission via mosquito, ZIKV is also sexually transmitted, which introduces the possibility that ZIKV infection could occur shortly after conception. However, the mechanisms underlying ZIKV-induced birth defects in early development are not understood. I hypothesize that sexually transmitted ZIKA virus infects embryos around the time of conception, leading to the most severe congenital defects. Consistent with this hypothesis, I have discovered that candidate proviral factors are present in mouse embryo-derived stem cell lines and preimplantation development. However, embryo-derived stem cell lines exhibited low viral infection and replication. Nevertheless, Puerto Rican (ZIKVPR) and the Ugandan (ZIKVUG) strains of ZIKV caused two-cell embryos to undergo developmental arrest. Moreover, infected blastocyst exhibited reduced SOX2 expression, an epiblast cell marker, CDX2 a trophectoderm cell marker, and SOX17, a primitive endoderm marker. Therefore, my results suggest that preimplantation ZIKV infection causes embryonic demise or embryonic cell fate defects depending on the time of infection. My studies are significant to human health because they will further our knowledge of viral infection in early pregnancy and the outcomes. Show less
