The Mechanisms of EBV Infection and Carcinogenesis, and Strategies for Prevention and Treatment
ZHANG Tao#, SUN Cong#, FENG Guokai, XU Miao, ZHONG Qian*, ZENG Musheng*
EBV (Epstein-Barr virus) infection is highly prevalent in the population and has been linked to various malignant tumors, including nasopharyngeal carcinoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, NK/T lymphoma, and others. These tumors have a significant impact on public health, underscoring the need for further research and intervention strategies. However, due to the unclear mechanism of infection and the lack of suitable epithelial cell infection models and animal models, no effective drugs or vaccines against EBV have been approved and marketed. This poses a significant challenge to the prevention and treatment of EBV. For this reason, considerable efforts have been focused on the study of EBV infection and intervention over the past two decades. This has involved establishing a model of NPECs (nasopharyngeal epithelial cells) susceptibility to infection, conducting an in-depth study of the EBV infection mechanism, and identifying NRP1, NMHC-IIA, and EphA2, along with other viral receptors. Additionally, the laboratory investigated and identified the oncogenic mechanism of EBV. The findings indicate that EBV transcription products, including LMP2A, LMP1, and BART2-5P, are associated with tumor formation, invasion, and metastasis. This provides a crucial scientific foundation for the prevention and treatment of EBV-related tumors. By analyzing EBV sequences, the laboratory has identified virus subtypes associated with a high risk of nasopharyngeal carcinoma, thereby establishing a foundation for subsequent vaccine development and tumor prevention. In recent years, the laboratory has conducted extensive research in the development of an EBV vaccine and the identification of efficient neutralizing antibodies. The contributions include the development of the Fc gp350 vaccine, the Fc gp350 dimer vaccine, the VLPs gp350 tripeptide vaccine, and the gp350 nanoparticle vaccine. Additionally, the laboratory has made significant advancements in the field of vaccine technology through the work on the VSV gB, gH/gL vaccine. The laboratory developed a gB nanoparticle vaccine, an mRNA therapeutic vaccine (trunc-LMP2A/EBNA1/EBNA3A), a gH/gL vaccine, a gB vaccine, and a gp42 cocktail nanoparticle vaccine as well. Additionally, the laboratory established a phage library of EBV antibodies and discovered a variety of highly effective neutralizing antibodies against gB, gH, and gp42, providing an important strategy for the prevention and treatment of EBV.