Epstein-Barr virus infection confers de-differentiation properties in nasopharyngeal epithelial cells

Abstract

Undifferentiated nasopharyngeal carcinoma (NPC) is an endemic type of cancer in Southern China and Southeast Asia. Epstein-Barr virus (EBV) infection is believed to be an etiological factor for its pathogenesis. Previous studies have shown that ectopic overexpression of EBV oncoproteins, including LMP1 and LMP2A, would lead to the inhibition of epithelial cell differentiation; however, so far no direct evidence shows the regulatory roles of EBV infection per se on the differentiation properties of nasopharyngeal epithelial (NPE) cells. Our preliminary findings revealed that infection of M81, an EBV strain derived from NPC, contributed to the differentiation-resistant growth phenotype in immortalized NPE cells in vitro. Tumors in vivo grown by EBV-negative tumorigenic NPE cells exhibited well-differentiated histological features, as compared to the EBV-positive counterparts, suggesting the inhibitory functions of EBV in epithelial cell differentiation. Mechanism study revealed the contribution of aberrant retinoid signaling in the differentiation-resistant growth phenotype of EBV-infected NPE cells. The findings in this pilot study provide molecular and translational insights in EBV infection-induced differentiation resistance in NPE cells.