Role of BamHI-A Rightward Frame 1 in Epstein-Barr Virus-Associated Epithelial Malignancies

Abstract

Epstein-Barr virus is a ubiquitous persistent virus, which is involved in the development of some human cancers. A licensed vaccine to prevent Epstein-Barr virus infection is lacking. BamHI-A rightward frame 1 is a viral protein specifically detected in both nasopharyngeal and Epstein-Barr virus-positive gastric cancers. It has been proposed that this viral protein confers cancer properties to infected epithelial cells and is involved in the escape of cancer cells from immune recognition. In this review, we summarize the properties of BamHI-A rightward frame 1 which confers cancer characteristics to infected epithelial cells. Thus, BamHI-A rightward frame 1 is a potential therapeutic target for the treatment of either Epstein-Barr virus (EBV)-positive nasopharyngeal or gastric cancers.

Epstein-Barr virus (EBV) infection is associated with a subset of both lymphoid and epithelial malignancies. During the EBV latency program, some viral products involved in the malignant transformation of infected cells are expressed. Among them, the BamHI-A rightward frame 1 (BARF1) is consistently detected in nasopharyngeal carcinomas (NPC) and EBV-associated gastric carcinomas (EBVaGCs) but is practically undetectable in B-cells and lymphomas. Although BARF1 is an early lytic gene, it is expressed during epithelial EBV latency, mainly as a secreted protein (sBARF1). The capacity of sBARF1 to disrupt both innate and adaptive host antiviral immune responses contributes to the immune escape of infected cells. Additionally, BARF1 increases cell proliferation, shows anti-apoptotic effects, and promotes an increased hTERT activity and tumor formation in nude mice cooperating with other host proteins such as c-Myc and H-ras. These facts allow for the consideration of BARF1 as a key protein for promoting EBV-associated epithelial tumors. In this review, we focus on structural and functional aspects of BARF1, such as mechanisms involved in epithelial carcinogenesis and its capacity to modulate the host immune response.