Abstract
Epstein-Barr virus (EBV) is closely linked to the development of a number of human cancers. EBV-associated malignancies are characterized by a restricted pattern of viral latent protein expression which is sufficient for the virus to both initiate and sustain cell growth and to protect virus-infected cells from immune attack. Expression of these EBV proteins in malignant cells provides an attractive target for therapeutic intervention. Among the viral proteins expressed in the EBV-associated epithelial malignancies, the protein encoded by the BamHI-A rightward frame 1 (BARF1) is of particular interest. BARF1 is a viral oncoprotein selectively expressed in latently infected epithelial cancers, nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBV-GC). Here, we review the roles of BARF1 in oncogenesis and immunomodulation. We also discuss potential strategies for targeting the BARF1 protein as a novel therapy for EBV-driven epithelial cancers.
Highlights
Epstein-Barr Virus (EBV) is a human gamma herpesvirus that infects more than 95% of the population worldwide
Upon initial infection of submucosal B-lymphocytes in the naso/oropharynx, EBV establishes a latent infection in memory B cells, with infected cells expressing a limited subset of viral latent proteins that allow the virus to persist while evading host immune attack [1,2]
BamHI-A rightward frame 1 (BARF1) transcripts are abundantly detected in the tissues of nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinomas (GC) [6,7,8,9]. ∆Np63α, an epithelial-specific transcription factor expressed in undifferentiated NPC cells, has been shown to transactivate the BARF1 promoter to regulate constitutive expression in EBV-positive epithelial malignancies [10]
Summary
Epstein-Barr Virus (EBV) is a human gamma herpesvirus that infects more than 95% of the population worldwide. EBV is linked to the development of several lymphomas and carcinomas in immunocompetent individuals These include endemic Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL), Non-Hodgkin lymphoma (NHL), NK/T cell lymphoma (NKTL) as well as nasopharyngeal carcinoma (NPC), and a subset of gastric carcinomas (GC). Given the strong association of EBV with these malignancies, EBV-encoded proteins expressed within the tumour have been considered as viable therapeutic targets. EBV can adopt various forms of latency (latencies I, II and III), which differ in their repertoire of latent proteins expressed and are largely determined by host cell factors. EBV efficiently infects and transforms primary B cells into lymphoblastoid cell lines (LCLs) Both LCLs and PTLD display type III latency, where all latent proteins are expressed. These forms of EBV latency in tumours are very fluid, and there is increasing evidence that proteins associated with the virus’s replicative cycle can be expressed in virus-associated tumours [1,2,3]
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