Mouse models of Zika virus infection-induced placenta and fetal brain damage

Zika virus (ZIKV) infection during pregnancy is associated with the development of Congenital Zika syndrome. The ZIKV epidemic in 2015 in South America exhibited an increased incidence of microcephaly cases in infants born to mothers who were infected during pregnancy, and infection in adults led to Guillain-Barré Syndrome. A growing body of literature demonstrates that the vertical transmission of ZIKV results in placental infection and injury. Further, ZIKV is transmitted to the fetus, specifically inducing apoptosis in neuronal progenitor cells, resulting in the development of microcephaly. This review summarizes recent advances in ZIKV infection, cell death, immune activation, and protective strategies in various mouse models. Specifically, we have reviewed recent studies on placental and fetal brain/head infections in mouse models, namely anti-IFNAR1 antibody-treated wild-type mice, Ifnar-deficient mice, Stat2-deficient mice, and humanized STAT2 knock-in mice. We also discussed the role of ZIKV infection-induced cell death, inflammation, interferon response, and associated immune-related outcomes in the placenta and fetal brain/head. Additionally, we have reviewed recent advances in the development of vaccine candidates and potential therapeutic agents that protect against ZIKV-induced placental and fetal brain damage in preclinical models. In summary, our review of literature highlights key pathogenic mechanisms that drive ZIKV-induced placental and fetal brain/head injury, and protective strategies against ZIKV infection.