Quantitative analysis of Epstein-Barr virus immediate-early proteins and evaluation of its clinical role especially in nasopharyngeal

鼻咽癌（Nasopharyngeal carcinoma，NPC）是一种具有明显地理和人群差异的上皮性肿瘤，血清学研究发现其与EB病毒（Epstein-Barr virus，EBV）相关，并通过检测NPC细胞中EB病毒DNA和EB病毒编码的RNA证实了这种关系。鼻咽癌患者常出现抗EB病毒衣壳抗原和早期抗原IgG和IgA抗体升高。EB病毒以潜伏形式存在于上皮细胞和B淋巴细胞中。各种刺激可以激活病毒。Z蛋白和R蛋白是EBV裂解周期的立即早期蛋白，它们通过反式激活几个早期启动子来控制病毒从潜伏周期到裂解周期的转换。但肿瘤的溶解周期有时是不完全的。Z蛋白和R蛋白的表达早于EA和VCA，因此抗Z、R抗体滴度是鼻咽癌诊断的敏感指标。用Western blotting和ELISA法检测了鼻咽癌、传染性单核细胞增多症（IM）、非霍奇金淋巴瘤（NHL）、头颈癌和健康对照者血清中抗Z、R蛋白的反应性，鼻咽癌患者治疗前血清中抗Z、R蛋白均呈高滴度，而3例无复发的鼻咽癌患者中仅1例（33%）呈阳性。IM患者均无抗Z、R抗体。一些其他疾病的患者也有抗Z，-R抗体，但滴度较低。与抗VCA抗体相比，抗Z、R抗体对NPC具有特异性，抗VCA抗体阴性的NPC患者抗Z、R抗体滴度高，抗VCA抗体滴度升高的NHL患者抗Z、R抗体阴性。提示抗Z，R抗体滴度可作为鼻咽癌的诊断指标。

Nasopharyngeal carcinoma (NPC), an epithelial tumor which is characterized by marked geographic and population differences in incidence, is found to be associated with Epstein-Barr virus (EBV) by serologic evidence, and the relationship was confirmed by the detection of EBVDNA and EB-encoded RNAs in NPC cells. Elevation of lgG and lgA antibodies against EBV viral capsid antigen and early antigen are often found in NPC patients. Serologic tests of these antibodies have been recognized astumor markers for NPC.EBV persists in a latent form in both epithelial cells and B lymphocytes. A variety of stimulation may activate a virus. The Z protein and the R protein, which are immediate early proteins of the EBV lytic cycle, control the switch of the virus from a latent to a lytic cycle by transactivating several early promoters. But a lytic cycle is sometimes incomplete in tumor. Z protein and R protein are expressed earlier than EA or VCA,so anti-Z,-R antibody titers will be more sensitive markers for NPC.Plasmid presenting BZLF1 or BRLF1 gene were produced, and Z protein and R protein were harvested. Sera from patients with NPC,infectious monomucleosis (IM), non-Hodgkin's lyumphoma (NHL), head and neck carcinoma and healthy controls are examined for its reactivity against Z and R protein by Western blotting and ELISA.NPC patients before treatment all indicated high anti-Z,-R antibody titers, whereas in three NPC patients without recurrence, only one (33%) was positive. IM patients all indicated no anti-Z,-R antibodies. Several patients of other diseases have anti-Z,-R antibodies, but their titers were low. In comparison with anti-VCA antibodies, ant-Z,-R antibodies were specific to NPC.A NPC patients whose anti-VCA antibodies were negative indicated high anti -Z,-R antibody titers, and a NHL patient who shows elevation of anti-VCA antibody titer was negative in anti-Z,-R antibodies. These findings suggest that the anti-Z,-R antibody titers are useful markers for NPC.