Updated project metadata. Zika virus (ZIKV) compromises the placental integrity infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection, are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in inflammation. The purpose of this work iis work aims to investigate CSTB, RAGE, and AXL receptor expression in ZIKV infected placental tissues at term. The hypothesis is that in ZIKV-infected placenta, there is overexpression of CSTB and increased inflammation affecting the RAGE and AXL receptor expression. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and Western Blot analysis were performed to analyze proteins and pathways affected by ZIKV infection in frozen placenta. Pathological The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblasts layer, and cell agglutination associated to with ZIKV infection of placental tissue. ZIKV infection was mostly localized to the trophoblast layer. There was a significant decrease in the expression of CSTB, RAGE and AXLCSTB, RAGE and AXL expression in ZIKV positive placenta. This downregulation can impair immune responses and facilitate virus penetration into the placenta. Results are consistent with our previous studies and literature of on ZIKV infection by activation ofng Inflammasome and Pyroptosis through caspase 1 upregulation and affecting the cellular structure, tissue remodeling, and cell differentiation by upregulation of tubulin beta and heat shock protein 27.