Addressing an Emerging Issue
Zika virus (ZIKV) is a mosquito-borne Flavivirus that can cause infections and clinical diseases in humans. Of particular concern are transplacental infections in pregnant women resulting in significant medical disorders including microcephaly (incomplete brain development) of the fetus and intrauterine growth restriction. The centre of the current epidemic is Latin America. However, numerous countries worldwide have reported ZIKV infections including the US and Canada. With the recent confirmation of sexual transmission, ZIKV has an alarming potential for further global spread. The pathogenesis of diseases is unknown, and there are no approved vaccines or therapeutics available. Furthermore, the existing experimental models and tools to study ZIKV infection are limited.
This project aims to develop an in vivo model of ZIKV infection. In ongoing experiments, it has been found that newborn pigs can be infected with ZIKV. The pilot study also suggests that fetal pigs are susceptible to ZIKV infection. Therefore, the project will establish a fetal pig model of ZIKV-induced microcephaly/other brain pathology and use genomics to compare whole gene expression in the brain of infected and healthy fetuses. It will also establish an ex vivo explant model of ZIKV infection in the human maternal and fetal placental compartments for subsequent genomics studies. As a result, the study will deliver models that will be extremely useful for testing potential mitigation strategies. The models and obtained genomics data will help demonstrate two related aspects of ZIKV infection, pathogenesis of brain and placental infection.
