Watry D, Hedrick J A, Siervo S, Rhodes G, Lamberti J J, Lambris J D, Tsoukas C D
Department of Biology, San Diego State University, California 92182.
J Exp Med. 1991 Apr 1;173(4):971-80. doi: 10.1084/jem.173.4.971.
The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated.
爱泼斯坦-巴尔病毒（EBV）可引发传染性单核细胞增多症，并且与某些人类癌症密切相关。该病毒被认为仅通过与补体第三成分（C3）片段也相互作用的受体（CR2/CD21）与B淋巴细胞和上皮细胞结合。然而，最近的证据对这一观点提出了挑战。我们使用生物素偶联的EBV和链霉亲和素-藻红蛋白以及荧光素偶联的抗T细胞抗体进行双色免疫荧光分析，结果表明CD1阳性、CD3暗淡（不成熟）的人类胸腺细胞表达功能性EBV受体。在四项重复实验中，EBV与胸腺细胞的结合率在8%至18%之间。这种相互作用具有特异性，未偶联的病毒、抗CR2抗体、聚集的C3以及病毒用于结合CR2的gp350病毒糖蛋白抗体的抑制作用都证明了这一点。通过在与病毒孵育短至12天或长达6周的胸腺细胞中存在游离型EBV-DNA来评估，EBV能够感染胸腺细胞。游离型DNA分析通过用与病毒DNA的第一个内部重复序列杂交的EBV-DNA探针进行Southern印迹来进行。通过用EBV免疫血清进行Western印迹评估，在受感染的胸腺细胞中检测到EBV核抗原1也支持了EBV基因组的存在。通过使用抗CR2和抗gp350抗体的阻断实验确定，EBV感染具有特异性。最后，胸腺细胞的病毒感染可与白细胞介素2协同作用，并诱导依赖淋巴因子的细胞增殖。鉴于先前报道的EBV阳性人类T细胞淋巴瘤病例，人们提出EBV可能参与了以前未被认识到但实际存在的T淋巴细胞癌症。
