Zika virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity, but the mechanisms by which this occurs are unknown. Flavivirus can deregulate the host proteome, especially extracellular matrix (ECM) proteins. We hypothesize that a deregulation of specific ECM proteins by ZIKV, affects placental integrity. Using twelve different placental samples collected during the 2016 ZIKV Puerto Rico epidemic, we compared the proteome of five ZIKV infected samples with four uninfected controls followed by validation of most significant proteins by immunohistochemistry. Quantitative proteomics was performed using tandem mass tag TMT10plex™ Isobaric Label Reagent Set followed by Q Exactive™ Hybrid Quadrupole Orbitrap Mass Spectrometry. Identification of proteins was performed using Proteome Discoverer 2.1. Proteins were compared based on the fold change and p value using Limma software. Significant proteins pathways were analyzed using Ingenuity Pathway (IPA). TMT analysis showed that ZIKV infected placentas had 94 reviewed differentially abundant proteins, 32 more abundant, and 62 less abundant. IPA analysis results indicate that 45 of the deregulated proteins are cellular components of the ECM and 16 play a role in its structure and organization. Among the most significant proteins in ZIKV positive placenta were fibronectin, bone marrow proteoglycan, and fibrinogen. Of these, fibrinogen was further validated by immunohistochemistry in 12 additional placenta samples and found significantly increased in ZIKV infected placentas. The upregulation of this protein in the placental tissue suggests that ZIKV infection is promoting the coagulation of placental tissue and restructuration of ECM potentially affecting the integrity of the tissue and facilitating dissemination of the virus from mother to the fetus.

寨卡病毒 (ZIKV) 感染通过损害胎盘完整性与胎儿异常有关，但发生这种情况的机制尚不清楚。黄病毒可以解除对宿主蛋白质组的调控，尤其是细胞外基质 (ECM) 蛋白。我们假设 ZIKV 对特定 ECM 蛋白的失调会影响胎盘完整性。我们使用在 2016 年 ZIKV 波多黎各流行期间收集的 12 个不同胎盘样本，将 5 个 ZIKV 感染样本的蛋白质组与 4 个未感染对照进行比较，然后通过免疫组织化学验证最重要的蛋白质。使用串联质量标签 TMT10plex™ Isobaric Label Reagent Set 和 Q Exactive™ Hybrid Quadrupole Orbitrap 质谱进行定量蛋白质组学。使用 Proteome Discoverer 2.1 进行蛋白质鉴定。p使用 Limma 软件的价值。使用 Ingenuity Pathway (IPA) 分析重要的蛋白质途径。TMT 分析表明，ZIKV 感染的胎盘有 94 种经过审查的差异丰富的蛋白质，其中 32 种更丰富，62 种更少。IPA 分析结果表明，45 种失调的蛋白质是 ECM 的细胞成分，16 种在其结构和组织中发挥作用。ZIKV 阳性胎盘中最重要的蛋白质是纤连蛋白、骨髓蛋白多糖和纤维蛋白原。其中，通过免疫组织化学在另外 12 个胎盘样本中进一步验证了纤维蛋白原，发现在 ZIKV 感染的胎盘中纤维蛋白原显着增加。