Feichtinger H, Li S L, Kaaya E, Putkonen P, Grünewald K, Weyrer K, Böttiger D, Ernberg I, Linde A, Biberfeld G
Department of Pathology, University of Innsbruck, Austria.
J Exp Med. 1992 Jul 1;176(1):281-6. doi: 10.1084/jem.176.1.281.
High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.
在感染猿猴免疫缺陷病毒SIVsm株后随访长达746天的25只食蟹猴(猕猴属)中,有10只发生了高级别恶性非霍奇金淋巴瘤,其中5例为淋巴母细胞性、3例为多形性、2例为免疫母细胞性。通过电子显微镜检查、用针对人类EBV的探针进行Southern印迹杂交以及与参与人类B细胞转化的EBV相关核抗原(EBNAs)相对应的抗原表达,证实这些淋巴瘤与一种爱泼斯坦-巴尔(EB)样食蟹猴B淋巴细胞嗜性疱疹病毒(CBLV)有关。免疫球蛋白基因重排和均一的EBV附加体的Southern印迹证明表明,所有淋巴瘤都是与CBLV相关的单克隆B细胞增殖。我们的研究结果表明,就临床、形态学、表型和基因型特征而言,这些肿瘤与获得性免疫缺陷综合征中与EBV相关的恶性淋巴瘤相对应。因此,SIVsm免疫缺陷食蟹猴对CBLV相关淋巴瘤发生的特殊易感性似乎是人类EBV相关淋巴瘤的一个有用模型。