Table 1.
Effect of viral oncogenic proteins on the Wnt signaling pathway
| Virus | Viral oncogenic protein | Molecular mechanism | References |
|---|---|---|---|
| HHV-8 | LANA | - Inhibition of p53 and retinoblastoma protein. Accumulation of nuclear β-catenin via interaction with GSK3β. vGPCR-mediated up-regulation of β-catenin and Wnt7a in epithelial cells | (16, 17) |
| EBV | LMP1 | - Inhibition of SIAH1 expression in B lymphoma cells and up-regulation of β-catenin. Increased cytoplasmic β-catenin and hyperplasia induction of epithelial cells. | (18) |
| LMP2 | -Inhibition of epithelial cell differentiation. Accumulation of β-catenin is in the cytoplasm. The methylation of Wnt signaling proteins. Up-regulated viral miRNAs that target Wnt signaling. Expressed EBV- miR‐BARTs that target Wnt signaling. | (19-21) | |
| HBV | HBx | -Disintegration of the E-cadherin complex with β-catenin, binding to APC and displacing β-catenin from the destruction complex, suppression of GSK3β activity, modulation of CTNNB1, APC, and AXIN1 gene expression. Silencing of SFRP1 and SFRP5 proteins. Insertion of the HBX gene into LINE1 elements and activation of Wnt signaling pathway. | (22-24) |
| HBc and other proteins | - Upregulation of the LEF-1, CCND1, and MYC genes, HBc can be bound to 41 Wnt pathway gene promoters. | (18, 25, 26) | |
| HCV | Core | -Induced expression of Wnt signaling proteins via SFRP1 hyper-methylation. Downregulation of the Wnt gatekeepers such as DKK1, SFRP3 and SFRP5. | (27-34) |
| NS5A | -Activation of the Wnt pathway via beta-catenin nucleus stability. Expressed c-myc proto-oncogene and DNA damaging. Modulation of cellular microRNA expressions such as miR-155. Epigenetic changes including Methylated DKK1 and SFRP2 genes, SFRP4 and RUNX3 genes in HCV positive subjects | (35-39) | |
| HTLV | Tax | - Nuclear stability of beta-catenin. Activation of the Wnt pathway through interaction with the Wnt proteins such as Wnt5a and leucine-rich disheveled (Dvl)-associated protein. Inhibition of GSK3β | (40-42) |
| HBZ | - Upregulation of the DKK1 gene in epithelial cells. Upregulating the Wnt5a gene | (41) | |
| HIV | Tat | -Interaction with TCF4 and inhibition of Wnt signaling. Induced DKK gene expression. | (43, 44) |
| Nef | -Interaction with β-catenin proteins and T-cell transmigration. | (45, 46) | |
| gp120 | -Upregulating BDNF expression in BV2 cells through the Wnt/β-catenin signaling. | (46) | |
| HPV | E6 and E7 | - Interaction with Rb and P53 proteins. Stimulating or enhancing Wnt/β-catenin signaling. Inducing β-catenin-TCF/LEF-mediated transcription. Upregulating proto-oncogenes MYC and CCND1. Dysregulation of the Wnt pathway via modulation of MYC, FZD, DKK, and WNT16 genes. | (47-53) |
| CMV | US28 | - Promoted intestinal adenomatosis and CCND1 and nuclear β-catenin expression. Increased β-catenin independent of the Wnt pathway. Coding viral miRNAs that target the β -catenin. Induced Wnt2, and WISP2 and reduced Wnt5a, LRP6, CCND1, MYC, and DKK gene expressions. | (54-58) |
| Adenovirus | E1 | -Dysregulation of the Wnt signaling pathway in fibroblast cells. | (59-61) |
| Enterovirus | Type 1 | -Modulation of the Wnt pathway through regulated expression of miRNAs. | (62) |
| Coxsackievirus | Targeting LRP6 and WRCH1 and promotion of β-catenin degradation. | (63) |