ZIKV can infect human term placentas in the absence of maternal factors

Abstract

Zika virus infection can result in devastating pregnancy outcomes when it crosses the placental barrier. For human pregnancies, the mechanisms of vertical transmission remain enigmatic. Utilizing a human placenta-cotyledon perfusion model, we examined Zika virus exposure in the absence of maternal factors. To distinguish responses related to viral infection vs. recognition, we evaluated cotyledons perfused with either active or inactivated Zika virus. Active Zika virus exposure resulted in infection, cell death and syncytium injury. Pathology corresponded with transcriptional changes related to inflammation and innate immunity. Inactive Zika virus exposure also led to syncytium injury and related changes in gene expression but not cell death. Our observations reveal pathologies and innate immune responses that are dependent on infection or virus placenta interactions independent of productive infection. Importantly, our findings indicate that Zika virus can infect and compromise placentas in the absence of maternal humoral factors that may be protective.

Understanding the Mechanism and Extent of Transplacental Transfer of (−)‐∆9‐Tetrahydrocannabinol (THC) in the Perfused Human Placenta to Predict In Vivo Fetal THC Exposure

“…Placentas ( n = 23) from term donors with no known history of tobacco or drug use were collected within 30 minutes of cesarean delivery (see Table for demographics). The perfusion system and procedure were as previously described with some modification to the experimental design 18–20 . Briefly, two cotyledons were excised from each placenta and cannulated for simultaneous single‐pass perfusion for 2–4 hours in both the intervillous space (maternal side) and the fetal main artery at rates of 10 and 4 mL/min, respectively.…”

“…The perfusion system and procedure were as previously described with some modification to the experimental design. [18][19][20] Briefly, two cotyledons were excised from each placenta and cannulated for simultaneous single-pass perfusion for 2-4 hours in both the intervillous space (maternal side) and the fetal main artery at rates of 10 and 4 mL/min, respectively. The perfusate consisted of oxygenated HBSS buffer containing 0.2% bovine serum albumin (BSA), 2,000 U/L sodium heparin, and 5 mg/mL gentamicin, buffered to pH 7.4 and maintained at 37 °C.…”

Multiomics Approach Reveals Serum Biomarker Candidates for Congenital Zika Syndrome

“…Liver expression contributes more than twice to non-CZS and CZS proteomes compared to bone marrow tissue, the second highest. The placenta and brain proteins detected in serum samples can be interesting targets for biomarkers, considering the ZIKV tropism for both tissues. , Notably, a higher number of proteins expressed by the brain tissue was observed in the ZIKV-infected groups when compared to the CTR. For example, heat shock protein HSP90-alpha (HSP90AA1) and alpha-synuclein (SNCA) proteins were exclusively identified in ZIKV-infected patients (CZS – and CZS + groups).…”

Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines

“…This results in fetuses and infants with various anomalies which are collectively termed congenital Zika syndrome (CZS) [3]. ZIKV can also establish a productive [4,5] and longlasting [6] infection in the placenta, targeting multiple cell types and resulting in placental pathology [7]. Dysfunction of the placenta can then occur, which can impact oxygen and nutrient exchange and result in additional adverse pregnancy outcomes, such as growth restriction and low birth weight of the newborn [8,9].…”