Identification and characterization of viral and cellular determinants of Zika virus vertical transmission

• Applicant: Dr. Pietro Scaturro
• Subject Area: Virology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499961789

In the past few years, Zika virus (ZIKV) has raised significant public health concerns due to its association with visceral and neurotropic diseases in newborns. ZIKV can infect uterine cells and transmit vertically from the pregnant mother to the fetus, causing several congenital malformations in the fetus including microcephaly and fetal demise. Despite its devastating outcomes, the cellular and viral determinants underlying ZIKV vertical transmission at the fetomaternal interface are still largely elusive. To study the complex virus-induced perturbations occurring during vertical transmission, a complex heterotypic system recapitulating the biology of the fetomaternal interface is needed. Here, we propose to systematically profile and functionally characterize key viral and cellular determinants critically required for ZIKV vertical transmission in both maternal and fetal compartments. Importantly, these experiments will exploit an innovative three-dimensional in vitro system of endometrial organoids and spheroids, alongside with different trophoblast culture models. Using a combination of state-of-the-art proteomics and functional genetics, we will characterize viral-induced perturbations at the maternal and fetal compartments separately to understand the molecular basis of ZIKV infection and vertical transmission in humans. Identified host proteins and pathways will be further investigated using functional genetic screens to assess their functional relevance for ZIKV replication. Altogether, this study will shed light on neglected mechanisms of vertical transmission by flaviviruses, identifying critical host targets with therapeutic or drug repurposing potential. In addition, these efforts will lay the foundations for the development of unique heterotypic organoids platforms, recapitulating the microphysiology of the fetomaternal interface and the placenta.

• DFG Programme: Research Grants
• International Connection: Thailand
• Partner Organisation: National Science and Technology Development Agency (NSTDA); National Innovation Agency; Program Management Unit for Human Resources ; and Institutional Development
• Cooperation Partner: Dr. Teerawat Wiwatpanit