Significant progress in the study of key factors mediating Epstein-Barr virus infection of nasopharyngeal epithelial cells

In the national key research and development program "protein machinery and life process regulation" key special "herpes virus infection and the functional mechanism of protein machinery in the process of disease" (2016YFA0502100) and "new protein machinery based on genomic instability in the development of tumors With the support of action, mechanism and intervention” (2017YFA0505600), significant progress has been made in the study of EB (Epstein–Barr) virus infection mechanism, revealing a new mechanism by which EphA2 mediates EBV entry into epithelial cells.

Epstein-Barr virus infection is closely related to the incidence of Burkitt's lymphoma, nasopharyngeal carcinoma and about 10% of gastric cancer, so the mechanism of elucidating EB virus-infected cells is particularly important for the prevention and treatment of EB virus-associated tumors.

Zeng Musheng, a research team at the Cancer Center of Sun Yat-sen University, found that epidermal growth factor promotes Epstein-Barr virus infection of nasopharyngeal epithelial cells. Gene expression profiling chip and RNA silencing technology were used to identify Ephrin Receptor A2 (EphA2), a host factor that plays a key role in Epstein-Barr virus infection of epithelial cells. The epithelial cells that knocked out EphA2 by Crispr/cas9 technology almost completely lost the ability to be infected with Epstein-Barr virus, and the neutralizing antibody of EphA2, the ligand EphrinA1 and the inhibitor 2,5-dimethylpyrrolylbenzoic acid were significantly blocked. Epstein-Barr virus infection, while overexpression of EphA2 significantly enhances Epstein-Barr virus infection. Mechanistic studies have shown that EphA2 can directly bind to EB viral glycoproteins gB and gH/gL and promote endocytosis and fusion of EB virus. This study revealed a new mechanism by which EphA2 mediates the entry of Epstein-Barr virus into epithelial cells, and further discovers multiple pathways that block Epstein-Barr virus infection, providing a new target for the intervention of Epstein-Barr virus-associated diseases. Related results were published in the journal Nature Microbiology on January 1, 2018. (Technology Department)

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