gamma型疱疹病毒诱发B细胞淋巴瘤的机制研究

人类γ型疱疹病毒Epstein Barr virus (EBV) 和Kaposi's sarcoma herpesvirus (KSHV)与B细胞淋巴瘤的发生紧密相关。在有免疫缺陷或抑制的人群中， 如HIV感染的病人、骨髓或器官移植的病人， γ型疱疹病毒感染诱发B细胞淋巴瘤的风险尤其大。由于人类γ型疱疹病毒不能感染其他动物，至今还没有一个可以从体内（in vivo）角度来研究人类γ型疱疹病毒体内病理机制的动物模型。为了了解γ型疱疹病毒在B细胞淋巴瘤中的调节作用和致癌机制，本项目将以与人类γ型疱疹病毒有高度同源性的小鼠疱疹病毒murine gammaherpesvirus 68 （MHV68）为模式病毒，并利用我们近期成功创建的通过MHV68转化小鼠胚胎细胞诱发B细胞淋巴瘤的小鼠模型，来研究γ型疱疹病毒在体内诱发B细胞淋巴瘤的分子机制，从而探索γ型疱疹病毒相关淋巴瘤的治疗策略。

Human gammaherpesviruses which include Epstein-Barr Virus (EBV) and Kaposi's Sarcoma herpesvirus (KSHV) are tightly associated with B-cell lymphomagenesis. Especially in the setting of immunodeficiency, such as HIV infection, bone marrow or organ transplant patients with immunosuppressive drug treatment, infections with gammaherpesviruses EBV or KSHV greatly increase the incidence of B-cell lymphomas. Due to the restrictive host species of human gammaherpesviruses, there is still no animal model available to study the pathogenesis of associated lymphomas. To understand the mechanism and oncogenesis of gammaherpesviruses in the development of B-cell lymphoma, this study will utilize murine gammaherpesvirus 68 (MHV68) which has been known to be a good candidate for the pathogenesis study of gammaherpesviruses because it shares high homologous genome organization with EBV and KSHV. We have recently developed a breakthrough mouse model, in which MHV68 immortalized fetal liver cells, developed into mature B cells and induced B-cell lymphomas when injected into immunideficient mice. This phenotype recapitulates human gammaherpesvirus-associated lymphomas which majorly occur in immunosuppressed patients. By using this mouse model, we will seek to elucidate the molecular mechanism underlying virus-host interaction of gammaherpesvirus-induced lymphomagenesis and explore the novel therapeutic strategies for gammaherpesvirus-associated lymphomas.