EBV infection of primary colonic epithelial cells causes inflammation, DDR and autophagy dysregulation, effects that may predispose to IBD and carcinogenesis

Abstract

EBV is a gammaherpesvirus strongly associated to human cancer. The virus has been shown to play a role also in inflammatory diseases, including IBD, in the context of which colon cancer more frequently arise. In this study, we show for the first time that EBV infects primary colonic epithelial cells (HCoEpC), promotes pro-inflammatory cytokine secretion and activates molecular pathways bridging inflammation and cancer, such as ERK1/2. These effects, occurring in the course of the lytic phase of the viral life cycle, led to DDR and autophagy dysregulation. Such cellular responses, playing a key role in the maintenance of proteostasis and genome integrity, are essential to prevent carcinogenesis. Interestingly, we found that the use of the demethylating agent 5-AZA could counteract most of the effects induced by EBV infection in HCoEpC, suggesting that DNA hyper-methylation may strongly contribute to viral-driven inflammation and colon cancer predisposition.

Keywords

• EBV
• IBD
• Colon cancer
• Cytokines
• ERK1–2
• Methylation