Development of a model animal for Epstein-Barr virus infection

人类CD21(HCD21)分子优先表达于B淋巴细胞，是EBV吸附的受体，这决定了EBV对B淋巴细胞的优势趋向性。来自人类和一些灵长类动物的B淋巴细胞，而不是来自其他物种的B淋巴细胞，对EBV感染很敏感。我们最近已经证明，hCD21基因的导入使一些犬和大鼠细胞对EBV感染易感，并可以从这些细胞中分离出稳定的EBV感染细胞克隆。这些结果表明，一旦最初的附着障碍被克服，EBV可以穿透并稳定地感染狗和大鼠的细胞。这一发现促使我们产生了一只携带hCD21基因的转基因大鼠，这可能成为EBV感染的动物模型。我们产生了由小鼠免疫球蛋白增强子驱动的表达人CD21基因(HCD21)的转基因大鼠。EB病毒潜伏基因的表达表明，表达hCD21的脾B淋巴细胞对EB病毒(EBV)感染易感，但这种感染是流产的，且不伴随原始细胞的生成、细胞DNA的合成或增殖。本研究结果表明，人和大鼠淋巴细胞在体外对EBV感染的反应是不同的。我们正在研究hCD21转基因大鼠能否成为EBV感染的模型动物。

The human CD21 (hCD21) molecule, which is preferentially expressed on B-lymphocytes, is the receptor for EBV adsorption, and this determines the predominant B-lymphocyte tropism of EBV. B-lymphocytes from humans and some primates, but not from other species, are susceptible to EBV infection. We have recently demonstrated that introduction of the hCD21 gene makes some canine and rat cells susceptible to EBV infection and stably EBV-infected cell clones could be isolated from these cells. These results suggest that once the initial barrier to attachment is overcome, EBV can penetrate into and stably infect canine and rat cells. This finding has prompted us to generate a transgenic rat with the hCD21 gene, which could become an animal model for EBV infection. We generated transgenic rats expressing the human CD21 gene (hCD21) driven by the mouse immunoglobulin enhancer. Spleen B-lymphocytes expressing hCD21 were susceptible to Epstein-Barr virus (EBV) infection as evidenced by EBV latent gene expression, but the infection was abortive and was not followed by blastogenesis, cellular DNA synthesis or proliferation. The present findings indicate that human and rat lymphocytes respond to EBV infection differently in vitro. We are now studying whether the hCD21 transgenic rat could become a model animal for EBV infection.