Zika virus (ZIKV) is a positive sense single strand RNA virus and a member of the Flaviviridae family. Infection of women during the 1st trimester of pregnancy can result in infection of the placenta and fetus, causing severe neurological defects and infant microcephaly. Most studies investigating placental infection have used immortalised cell lines or term placental tissues which may not accurately reflect 1st trimester placental responses. Here we investigate ZIKV infection and the resulting host cellular innate immune response in 1st trimester tissue explant cultures and primary villous cytotrophoblasts (CTBs).
Placentas were obtained with informed consent from women undergoing elective pregnancy termination. Tissue sections were either cultured in Matrigel as tissue explants or used to isolate CTBs by digestion and negative magnetic dynabead purification. Both CTB and explant cultures were infected with ZIKV (PRVABC59) and samples analysed 24, 48 or 72 h post infection by 1) immunocytochemistry, 2) qRT-PCR and 3) plaque assay. We demonstrate robust infection and production of infectious ZIKV in both explant and CTB cultures. Interestingly, even in the face of significant ZIKV replication, the cellular ISG response was significantly attenuated suggesting that either ZIKV blocks the early innate response or that these cultures are unresponsive at the innate immune level. However, stimulation of CTBs with polyI:C revealed a robust innate response suggesting they are innate immune competent. These results show that the 1st trimester placenta is susceptible to ZIKV infection but infection does not induce an effective innate antiviral response. This may facilitate an environment favourable to ZIKV replication and dissemination to the fetal tissue, in turn causing the devastating pathologies associated with congenital Zika virus syndrome.