Table 3.
Main characteristics related to molecular analysis
| Study ID | Sample size | Time-point of the molecular analysis | Molecular evaluation | Genes | Method | Sample | Molecular alterations due ZIKV infection | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Exposed | Control | Pathway/biological function | Upregulated genes | Downregulated genes | ||||||||||
| Li et al., 2016 [18] | 2/3 embryos for each dam | 1/3 embryos for each dam | 3 dpi (E16.5) | Transcriptome | – | RNA-seq | Whole brain | Upregulation of immune-response (especially genes related to cytokine production and the response to cytokines) and apoptosis pathways (e.g., STAT1, STAT2, TRIM21, TRIM25, IFIT1, IFIT2, IFIT3, TLR3 TLR7, TLR9, CCL2, CCL3), antiviral response genes (e.g., TLR3, DDX58, IFIH1, OAS2, IRF7, ISG15, MX1, CCL5, CXCL10, IFNB1) and flavivirus entry receptors (e.g., AXL); downregulation of microcephaly-associated genes (e.g., ASPM, CASC5, CENPF, MCPH1, RBBP8, STIL, TBR2) | 510 genes (logFC > 0.26) | 95 genes (logFC < − 0.26) | ||||
| Shao et al., 2016 [32] | 3 embryos | 3 embryos | 3 dpi (E17.5) | Transcriptome | – | RNA-seq | Brain | Upregulation of immune response and apoptosis pathways (e.g., OASL2, USP18, IFIT1, MX2, OAS1BIFIT3, IIGP1, DDX60, IFI44, IRF7, TLR3, CASP8) | 197 genes (logFC > 1.52) | 3 genes (logFC = − 2.22) | ||||
| Vermillion et al., 2017 [33] | 10 placentas (inoculated at E10) | 6 placentas (E10) + 6 (E14) | 2 dpi (E12) | Candidate genes | MERTK, AXL, and GAS6 | RT-qPCR | Placenta | TAM receptors and Interferon-inducible genes | MERTK, AXL and GAS6; ISG15, IFITM3, and OAS1B | – | ||||
| ISG15, IFITM3, and OAS1B | ||||||||||||||
| Yockey et al., 2018 [25] | For ISG: 6 placentas and 6 fetuses from 3 infected litter | 4 placentas and 4 fetuses from 1 litter | 9 dpi (E17.5) | Candidate genes | OASL2, MX1, and USP18 | RT-qPCR | Placenta and embryos | Interferon-inducible genes (ISG) | OASL2, MX1, and USP18 in placentas and fetuses | – | ||||
| For HRG: 9 fetuses per genotype | 3 Ifnar1−/− and 5 Ifnar1+/− fetuses | 5 dpi (E10.5) | VEGFA, ADM, BNIP3, PFKFB3, and GLUT1 | Placenta | Hypoxia response genes (HRG) | VEGFA, ADM, BNIP3, PFKFB3, and GLUT1 in fetuses | ||||||||
| Khaiboullina et al., 2019 [34] | 6 embryos ZIKV + in the brain | 21 embryos | 13 dpi (GD 17.5) | Candidate genes | IL-1, IL-6, IL-18, CCL2, CXCL1, CXCL10, MX1, TLR7, and TNFΑ | RT-qPCR | Brain and placenta of embryos | Inflammatory factors | MX1, CCL2, CXCL1, and CXCL10 and modest increase of TLR7, IL-1β, IL-6, IL-18, and TNFΑ (ZIKV + in the brain) (without p-value) | - | ||||
| 8 embryos ZIKV − in the brain | TLR7, CCL2, CXCL1, IL-18, and IL-6 and modest increase of MX1, CXCL10, IL-1β, and Tnfα (ZIKV + placentas) (without p-value) | |||||||||||||
| Rathore et al., 2019 [35] | 5 mouse brains | 5 mouse brains | 11 days (E18) | Candidate genes | BRN1, BRN2, OTX1, OTX2, EMX2, PAX6, and FOXG1 | RT-qPCR | Brains | Cortical neurogenesis | – | BRN1, BRN2, OTX1, OTX2, FOXG1, and PAX6 | ||||
| Westrich et al., 2021 [36] | 3–5 (mouse) | 3–5 (mouse) | 3 days (E15) | Candidate genes | Cxcl10 | RT-qPCR | Placenta and fetal tissue | Inflammatory response | Cxcl10 | – | ||||
| 3–7 (guinea pig) | 3–7 (guinea pig) | 3 days (E24) | ||||||||||||
| Darbellay et al., 2017 [20] | 5 embryos | 6 embryos | 28 dpi (GD 78) | Transcriptome | – | RNA-seq | Cerebral and cerebellar cortex | Upregulation of antiviral response and interferon production pathways (e.g., OAS1, STAT1, IGS12A, IFITM1, IFIH1, IRF9, DDS60, IFIT3, OAS2, MX1); Downregulation of mitosis associated genes (e.g., CCNB1, CDC1, TP53) | 323 genes = logFC > 0.35 | 33 gene = logFC < –0.29 | ||||
| Thawani et al., 2018 [24] | 10 embryos | 10 embryos | 3 dpi (E5) | Candidate genes | BMP7, FFG8B, SHH, and PTCH1 | in situ hybridization | Brain | Brain-related morphogens | – | BMP7, FGF8B, SHH, and PTCH1 | ||||
dpi: days post infection; E: embryonic day; GD: gestational day; RNA-seq: transcriptome; RT-qPCR: reverse transcriptase-quantitative Polymerase Chain Reaction; logFC: logarithm fold change