Transcriptomics analysis of trimester-specific full-term placentas from three Zika virus-infected women

Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. In this study, full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Nevertheless, these findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients. Overall design: Three ZIKV-positive pregnant women were recruited to the study, who had been infected with ZIKV in different trimesters following the ZIKV outbreak that happened in Singapore in 2016. Transcriptome profiling of the placenta discs and foetal membranes of the placentas was used to investigate the cellular host response during ZIKV infection. Both tissues were digested to obtain a single-cell suspension: the placenta disc was further separated into CD45+ immune and CD45- non-immune fractions, to define the drivers of ZIKV-induced cellular changes. Tissue samples were collected in triplicate to account for tissue heterogeneity, except those obtained from Patient 3, where the sample was processed as a whole, due to technical difficulties. Placental samples from two healthy women were included as controls.