SUMMARY / ABSTRACTThe outbreak of Zika virus (ZIKV) and the alarming rise in fetal brain malformations highlight ZIKV as an urgentpublic health concern. ZIKV has recently met Shephard's criteria for teratogenic classification because of thebrain anomalies reported. This application addresses the direct relationship between ZIKV infection and fetalbrain development using our established fetal primate model of intrauterine pathogenesis. The studies outlinedin this application leverage our prior discoveries and collaborative investigations on neural precursor cellfunction in relation to microglia in the fetal primate brain, and our expertise in primate development, imaging,virology, and immunology. Our track record and experienced team provides the means to pursue the goals ofthis proposal?understanding the mechanism(s) of ZIKV teratogenesis?and the steps necessary to progressto studies focused on interventions. Our goal is to determine how ZIKV alters cortical development bycapitalizing on our team's essential expertise and research experiences to address this urgent public healthconcern rapidly and effectively through the following Specific Aims: (1) Define the impact of fetal ZIKV onneural precursor cells and cortical development, and (2) Determine the impact of fetal ZIKV infection on fetaland maternal inflammation and assess if inflammation is predictive of abnormalities in cortical development.These studies will provide new insights into the underpinnings of ZIKV teratogenesis in a primate model withsimilar neurodevelopmental features when compared to humans, and by efficiently leveraging an existingprimate model of fetal viral infection. Overall, these investigations focus on fetal developmental outcomesassociated with direct ZIKV infection and will provide the necessary mechanistic understanding and outcomemetrics to assess intervention strategies that protect the fetus and newborn from the devastatingconsequences of ZIKV infection and congenital disease.
|Effective start/end date||8/1/16 → 7/31/18|
- National Institutes of Health: $193,000.00