An oncogenic role for EBV-encoded BILF1 in nasopharyngeal carcinoma

It is widely recognized that latent infection is the predominant mode of Epstein–Barr virus (EBV) infection in nasopharyngeal carcinoma (NPC) in which a specific set of latent genes is responsible for driving the development of the disease. However, the expression of these latent genes does not adequately explain the various transformed phenotypes of NPC cells. Using an established high-throughput quantitative reverse transcription PCR array, we found that several EBV lytic genes were more widely expressed in primary NPC tissues than previously recognized. We focused on a lytic gene, BILF1, which encodes a constitutively active G protein-coupled receptor (GPCR). We showed that BILF1 was expressed in tumour cells from primary NPC tissues at both mRNA and protein levels, and in the absence of BZLF1 expression. RNA sequencing analysis of BILF1-expressing immortalised nasopharyngeal epithelial (NPE) cells demonstrated that the profile of BILF1-regulated genes significantly overlapped with gene signatures of micro-dissected NPC, indicating that the expression of BILF1 is relevant to the pathogenesis of NPC. In accordance with these observations, pathway analysis of the transcriptome of BILF1-expressing cells showed the involvement of BILF1 in key biological processes typically deregulated in NPC. To examine whether BILF1 expression influenced epithelial cell behaviour, functional studies showed that BILF1 enhanced cell proliferation, migration, invasion and colony formation. In addition, BILF1 increased AKT activation in NPE cells, which was responsible for the increase in cell migration. Taken together, our data convincingly point to an oncogenic role for BILF1 in NPC.