RNA-Seq Reveals Transcriptome Changes Following Zika Virus Infection in Fetal Brains in c-Flip Knockdown Mice

The FADD-like interleukin-1β converting enzyme (FLICE)-inhibitory protein (c-FLIP) plays a crucial role in various biological processes, including apoptosis and inflammation. However, the complete transcriptional profile altered by the c-FLIP is not fully understood. Furthermore, the impact of the c-FLIP deficiency on the transcriptome during a Zika virus (ZIKV) infection, which induces apoptosis and inflammation in the central nervous system (CNS), has not yet been elucidated. In this study, we compared transcriptome profiles between wild-type (WT) and the c-Flip heterozygous knockout mice (c-Flip^+/-) fetal heads at embryonic day 13.5 from control and PBS-infected WT dams mated with c-Flip^+/- sires. In the non-infected group, we observed differentially expressed genes (DEGs) mainly involved in embryonic development and neuron development. However, the ZIKV infection significantly altered the transcriptional profile between WT and the c-Flip^+/- fetal heads. DEGs in pattern recognition receptor (PRR)-related signaling pathways, such as the RIG-I-like receptor signaling pathway and Toll-like receptor signaling pathway, were enriched. Moreover, the DEGs were also enriched in T cells, indicating that the c-FLIP participates in both innate and adaptive immune responses upon viral infection. Furthermore, our observations indicate that DEGs are associated with sensory organ development and eye development, suggesting a potential role for the c-FLIP in ZIKV-induced organ development defects. Overall, we have provided a comprehensive transcriptional profile for the c-FLIP and its modulation during a ZIKV infection.