Table 1 Possible carcinogenic mechanisms of viruses implicated in childhood cancers
From: Childhood cancers: what is a possible role of infectious agents?
Virus and its product | Mechanism | Reference |
|---|---|---|
| Â | Inhibition of apoptosis | Â |
- EBV | Â | Â |
 ➢ EBNA-1 | - Related to BCL2 | [16] |
 ➢ BHRF1, BALF1 | - Related to BCL2 | [17] |
 ➢ EBNA3A, 3C | - Inhibit Bim | [18] |
- CMV | Â | Â |
 ➢ IE1, IE2 | - Inhibit apoptosis by activating PI3K pro-survival pathway | |
 ➢ UL36 | - Confers resistance to chemotherapy in neuroblastoma | [29] |
| Â | Disruption of signaling pathways/autonomous growth | Â |
- HHV-6 (U95) | - U95 binds NF-kB, probably deregulating the pathway | [30] |
- EBV | - JAK/STAT pathway implicated L6 released by macrophages surrounding nasopharyngeal epithelial cells, binds to its receptor and activates STAT3, which triggers transcription of its target genes (cyclin D1, Bcl-xL, c-myc, survivin, VEGF). A correlation of VEGF expression as a key angiogenic factor in NPC metastasis is supported. | |
[22] | ||
- SV40 | - Activation of growth factors and autocrine growth of mesothelioma cells, while RASSF1 is inactivated | [31] |
| Â | Ablation of tumor-suppressors p53: viral proteins bind and thereby inactivate the tumor suppressors | Â |
- HPV 16/18 (E6, E7) | - Bind and inactivate p53 | [32] |
- BKV | - BKV is present in neuroblastomas, and colocalizes to p53. | [33] |
- HHV-6 (U14 and ORF-1) | - Bind and inactivate p53 | [30] |
| Â | Promotion of epigenetic changes/RNA interference | Â |
- EBV | - EBV-infected cells acquire extensive methylation to silence multiple tumor suppressor genes. | [23] |
 ➢ LMP1 | - LMP1 downregulates CDH1 0.2-fold through upregulation of DNMT1, DNMT3A, DNMT3B, and 3-8-fold in NPC076 NPC cell line. | [24] |
 ➢ miR-BART5 | - Downregulation of PUMA expression in EBV-positive NPC and gastric carcinoma cells; decreasing levels of miR-BART5 or expression of PUMA can revert the suppression of apoptosis. | [25] |
| Â | Suppression and evasion of the immune system | Â |
- CMV | - Inhibit expression of HLA class I and II antigens and antigen presentation, thus activation of T-cells | [34] |
- EBV (EBNA-1) | - Cells expressing EBNA-1 do not present sufficient quantities of EBNA1 peptide on MHC class I. | [26] |