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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
  Inhibition of apoptosis  
- EBV   
 ➢ EBNA-1 - Related to BCL2 [16]
 ➢ BHRF1, BALF1 - Related to BCL2 [17]
 ➢ EBNA3A, 3C - Inhibit Bim [18]
- CMV   
 ➢ IE1, IE2 - Inhibit apoptosis by activating PI3K pro-survival pathway [27, 28]
 ➢ UL36 - Confers resistance to chemotherapy in neuroblastoma [29]
  Disruption of signaling pathways/autonomous growth  
- 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. [1921]
- SV40 - Activation of growth factors and autocrine growth of mesothelioma cells, while RASSF1 is inactivated [31]
  Ablation of tumor-suppressors p53: viral proteins bind and thereby inactivate the tumor suppressors  
- 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]
  Promotion of epigenetic changes/RNA interference  
- 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]
  Suppression and evasion of the immune system  
- 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]