Sairenji T, Reisert P S, Spiro R C, Mulder C, Humphreys R E
Hematol Oncol. 1983 Jul-Sep;1(3):251-62. doi: 10.1002/hon.2900010307.
We tested the hypothesis that Epstein-Barr virus (EBV) might actually infect leukemic hairy cells in vivo by examining those cells for the EBV-receptor, EBV nuclear antigen (EBNA) and membrane antigen (MA), for spontaneous transformation and rescue of infectious virus and for presence of EBV genome. EBV-receptors were found on subpopulations of leukemic cells from each of 7 patients with hairy cell leukemia (HCL) tested. MA was present on low numbers (1-5 per cent) of fresh leukemic cells of 7 patients and in some instances occurred with a greater frequency after 3 to 5 days in culture, with or without 12-O-tetradecanoylphorbol-13-acetate. In 11 fresh leukemic cell preparations from 8 HCL patients, no EBNA was demonstrated. However, 2 samples after 4 days in culture expressed low frequencies of EBNA-positive cells. Spontaneous, EBV-positive cell lines were established with a high transformation efficiency from 3 HCL blood samples but not from 8 other specimens. Infectious EBV could be rescued from some hairy leukemic cell preparations by co-cultivation with cord blood lymphocytes. These results demonstrated that leukemic cell populations harbored infectious EBV, that the leukemic cells expressed virus receptors and suggested that a small subpopulation of leukemic cells might become infected in vivo at least transiently and possibly transformed in vitro by EBV. To test for the extent of occult in vivo infection of leukemic cells with EBV, Southern type hybridization studies were performed with a probe for EBV genome (Bam HI W). At a sensitivity level of 0.1 genome per cell, EBV genome was not detected in the leukemic cell populations of 7 patients. We conclude that host defence mechanisms protecting these individuals from EBV also prevent infections of the leukemic cell and/or most hairy leukemic cells are not suitable targets for both infection and transformation.
我们通过检测白血病毛细胞中的EB病毒（EBV）受体、EBV核抗原（EBNA）和膜抗原（MA），检测其自发转化及传染性病毒的拯救情况，以及检测EBV基因组的存在，来验证EBV可能在体内实际感染白血病毛细胞这一假说。在检测的7例毛细胞白血病（HCL）患者的白血病细胞亚群中均发现了EBV受体。MA存在于7例患者新鲜白血病细胞中的少数细胞（1%-5%）中，在某些情况下，培养3至5天后，无论有无12-O-十四烷酰佛波醇-13-乙酸酯，其出现频率都会更高。在8例HCL患者的11份新鲜白血病细胞制剂中，未检测到EBNA。然而，2份培养4天后的样本中出现了低频率的EBNA阳性细胞。从3份HCL血样中以高转化效率建立了自发的EBV阳性细胞系，但8份其他样本未建立。通过与脐血淋巴细胞共培养，可从一些毛细胞白血病细胞制剂中拯救出传染性EBV。这些结果表明，白血病细胞群体中存在传染性EBV，白血病细胞表达病毒受体，提示一小部分白血病细胞可能至少在体内短暂感染，并可能在体外被EBV转化。为了检测白血病细胞在体内被EBV隐匿感染的程度，用EBV基因组探针（Bam HI W）进行了Southern杂交研究。在每个细胞基因组含量为0.1的检测灵敏度水平下，7例患者的白血病细胞群体中均未检测到EBV基因组。我们得出结论，保护这些个体免受EBV感染的宿主防御机制也能防止白血病细胞感染，和/或大多数毛细胞白血病细胞不是感染和转化的合适靶点。
