Abstract
Simple SummaryEpstein–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.
Highlights
The human gammaherpesvirus-4 (HHV-4), commonly referred to as Epstein–Barr virus (EBV), is a member of the Herpesviridae family and Lymphocryptovirus genus [1]
This lytic gene is highly expressed in nasopharyngeal carcinomas (NPC) and EBV-associated gastric (EBVaGC) carcinomas during latency [11,12], but is virtually undetectable in B-cells and lymphomas, in which it can mostly be found during the viral lytic cycle [13,14]
BamHI-A rightward frame 1 (BARF1) is an early lytic viral protein highly expressed in latently EBV-infected epithelial viral carcinogenesis
Summary
The human gammaherpesvirus-4 (HHV-4), commonly referred to as Epstein–Barr virus (EBV), is a member of the Herpesviridae family and Lymphocryptovirus genus [1]. Among the EBV proteins involved in the malignant transformation of epithelial cells, the BamHI-A rightward frame 1 (BARF1) is of utmost importance [10] This lytic gene is highly expressed in nasopharyngeal carcinomas (NPC) and EBV-associated gastric (EBVaGC) carcinomas during latency [11,12], but is virtually undetectable in B-cells and lymphomas, in which it can mostly be found during the viral lytic cycle [13,14]. This fact allows for the consideration of BARF1 as an epithelial-specific EBV oncogene as well as an attractive potential therapeutic target for EBV-associated epithelial tumors [15]. A model of BARF1 mediated carcinogenesis in epithelial cells is proposed
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