Proteomic profiles of Zika virus‐infected placentas bearing fetuses with microcephaly

Abstract

Purpose Zika virus (ZIKV) transmission to the fetus during pregnancy could enable a collection of severe fetal malformations like microcephaly (MC), termed Congenital Zika Syndrome (CZS). The mechanisms involved in ZIKV transplacental transmission are not fully understood. Experimental Design Here we aim to identify in placental tissues the deregulated proteins associated with ZIKV‐induced MC using label‐free proteomics. Results We found proteins associated with DNA damage and gene expression inhibition up‐regulated in infected placentas with no MC fetuses (Z+) compared to the control group (Ctr). Actin filament organization and the immune response were also found deregulated in the Z+ group. In ZIKV‐positive placentas bearing fetuses with MC (MC+) was detected an increase in T cell activation, indicating an elevated immune response. A comparison between MC+ and Z+ groups showed a higher abundance of proteins related to endocytosis and autophagy in MC+, suggesting a higher transcytosis of vesicles with ZIKV particles across the maternal‐fetal interface. Conclusions and Clinical Relevance Our results suggest that higher expression of integrins in MC+ might be associated with high internalization of the virus since these proteins are known as virus receptors. Similarly, an increased immune response in the placenta and higher infiltration of the virus to the fetus could contribute to the neurological malformation of the CZS.

HLA-A, HSPA5, IGFBP5 and PSMA2 Are Restriction Factors for Zika Virus Growth in Astrocytic Cells

“…Numerous proteomic and transcriptomic studies have been conducted to explain ZIKV infection in microcephalic fetuses, primary human fetal neural progenitor cells, serum samples, placental tissues, and astrocyte-derived cell lines [ 45 , 46 , 47 , 49 ]. This study identified numerous cellular proteins, some of which were similar to previous studies while others were novel.…”

“…Among the similarities, fibronectin was found to be downregulated by ZIKV in U251 cells in this study. Our previous SOMAScan proteomic study also implicated ZIKV-induced damage to placental integrity [ 45 , 54 ]. Cytokines and chemokines such as IL-6 were identified as downregulated while IL-8 and CCL5 were upregulated in this study ( Table 2 ) and in our previous study [ 54 ].…”

“…Numerous mass spectrometry studies have been conducted in numerous cell types to examine host protein modifications after ZIKV infection. A label-free approach using LC-MS/MS in microcephalic fetuses found patterns of dysregulations in DNA damage repair response and mRNA translation to be linked with ZIKV infection [ 45 ]. Another TMT 10-plex study on placental tissues associated ZIKV infection with placental integrity compromise [ 46 ].…”

A Capsid Protein Fragment of a Fusagra-like Virus Found in Carica papaya Latex Interacts with the 50S Ribosomal Protein L17

“…Proteome Discoverer software version 2.1 (Thermo Fisher Scientific, Waltham, MA, USA) was employed for the raw data processing. Protein identification was carried out according to Quiñones-Vega et al [ 22 ]. Three protein databases were used (all downloaded in September 2022): (i) Arabidopsis thaliana UniProt database ( ), accessed on 29 September 2022), (ii) plant viruses + taxonomy_id:33090 + PMeV from Uniprot database ( ), accessed on 29 September 2022), and (iii) Carica papaya NCBI database ( Carica papaya ) AND “ Carica papaya ”[porgn:__txid3649].…”

Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development

“…Here, we achieve a comprehensive analysis between the AF metabolomics data and our previous AF, placenta, and brain proteomics data [14,15,47] from a broad perspective of the molecular pathways in common. In our ZIKV-infected placenta proteomics study [47], fatty acid synthase was increased four times in concentration in the microcephalic fetuses, which suggests an enhanced fatty acid synthesis to use in viral replication [23]. Interestingly, ATP synthase and ADP/ATP translocase presented a decreased concentration in microcephalic fetuses, which could be related to mitochondrial dysfunction caused by fatty acid accumulation [48].…”