Fig. 2

E5 immune evasion mechanisms. E5 induces COX-2 expression through: i) the activation of the epidermal growth factor receptor (EGF-R) signalling pathway and the interaction with the nuclear factor 1 (NF-1), which results in the induction of ii) AP-1 and iii) NF-κB transcription, which has the strongest effect on COX-2 transcription. E5 upregulation of EGF-R expression also leads to an increase of the vascular endothelial growth factor (VEGF), through COX-2 [48]. Following this, COX-2 and EP4 stimulate PGE2 signalling pathway through a feedback mechanism involving increased levels of cAMP, PKA and CREB (cyclic adenosine monophosphate response element binding protein), binding to the EP4 promoter [53]. This leads to a rise in the expression of this receptor [87, 88], which is associated with breast and colon carcinogenesis [145, 146]. Moreover, E5 impairs MHC I [36] and II [44] surface cell expression