Pallesen G, Hamilton-Dutoit S J, Rowe M, Lisse I, Ralfkiaer E, Sandvej K, Young L S
Laboratory of Immunohistology, University Institute of Pathology, Aarhus Kommunehospital, Denmark.
J Pathol. 1991 Dec;165(4):289-99. doi: 10.1002/path.1711650404.
Epstein-Barr virus (EBV) infection in lymphoproliferative lesions has been assumed to be strictly latent. In order to investigate the possible occurrence of EBV replication in AIDS-related lymphoma (ARL) cells, we studied 13 cases by immunohistology using monoclonal antibodies to the EBV-encoded switch-protein BZLF1, early antigens (EAs), late replicative proteins [virus capsid antigens (VCAs) and membrane antigens (MAs)], and to the latent proteins EB nuclear antigen 2 (EBNA 2) and latent membrane protein (LMP). EBV genomes were detected by in situ hybridization. EBV genomes and/or gene products were demonstrated in ten cases, including all immunoblast-rich lymphomas, two Burkitts lymphomas, and a T-cell anaplastic large-cell lymphoma. The BZLF1 protein, which disrupts latency in B cells, was identified in six (60 per cent), and EAs in four (40 per cent) of the EBV-positive ARL. Only one lymphoma (10 per cent) expressed VCAs and MAs. EBNA 2 and LMP were detected in three (30 per cent) and eight (80 per cent) of EBV-positive cases, respectively. EBV DNA was detected in lymphoma cells in 7 of 12 (58 per cent) cases. The most important finding of this study was frequent spontaneous activation of latent EBV in ARL. Production of complete virus, however, was either aborted, or tumour cells expressing late productive cycle proteins (VCA, MA) were rapidly cleared from tissues. It is suggested that host factors that normally inhibit replication of EBV are deficient in AIDS patients.
在淋巴增殖性病变中，爱泼斯坦 - 巴尔病毒（EBV）感染一直被认为是严格潜伏的。为了研究EBV在艾滋病相关淋巴瘤（ARL）细胞中可能发生的复制情况，我们使用针对EBV编码的开关蛋白BZLF1、早期抗原（EAs）、晚期复制蛋白[病毒衣壳抗原（VCAs）和膜抗原（MAs）]以及潜伏蛋白EB核抗原2（EBNA 2）和潜伏膜蛋白（LMP）的单克隆抗体，通过免疫组织学方法研究了13例病例。通过原位杂交检测EBV基因组。在10例病例中检测到EBV基因组和/或基因产物，包括所有富含免疫母细胞的淋巴瘤、2例伯基特淋巴瘤和1例T细胞间变性大细胞淋巴瘤。在6例（60%）EBV阳性的ARL中鉴定出了破坏B细胞潜伏状态的BZLF1蛋白，4例（40%）中检测到EAs。只有1例淋巴瘤（10%）表达了VCAs和MAs。在EBV阳性病例中，分别有3例（30%）和8例（80%）检测到EBNA 2和LMP。12例中有7例（58%）在淋巴瘤细胞中检测到EBV DNA。本研究最重要的发现是ARL中潜伏EBV频繁自发激活。然而，完整病毒的产生要么被中止，要么表达晚期生产周期蛋白（VCA、MA）的肿瘤细胞迅速从组织中清除。提示在艾滋病患者中，正常抑制EBV复制的宿主因素存在缺陷。
