Maintenance of Epstein-Barr virus latency through interaction of LMP2A with CXCR4.

Abstract

Epstein-Barr virus (EBV) belongs to the subfamily Gammaherpesvirinae and was the first human tumor virus to be discovered. The global rate of EBV infection in adults exceeds 90%. EBV can participate in the regulation of multiple genes and signal pathways through its latency genes. Many studies have shown that CXCR4 is involved in the development of gastric cancer, but there have been few studies on the specific mechanisms involved in EBV-associated gastric cancer (EBVaGC). In this study, we explored the mechanism by which EBV-encoded products maintain latent EBV infection through interaction with CXCR4 and investigated the role of CXCR4 in EBV-positive cells. The results show that there is a positive feedback between the EBV-encoded products and CXCR4, and LMP2A can activate CXCR4 through the NF-κB pathway. In addition, CXCR4 can be fed back to LMP2A and EBNA1 through the ERK signaling pathway. At the same time, CXCR4 can promote the proliferation and migration of EBV-positive cells, reduce the expression of the immediate early protein BZLF1, the late protein EBV gp350, and the viral capsid antigen, and play an important role in maintaining the incubation period of EBV infection. These findings are applicable to the further targeted therapy of EBVaGC.