Kasahara Y, Yachie A, Takei K, Kanegane C, Okada K, Ohta K, Seki H, Igarashi N, Maruhashi K, Katayama K, Katoh E, Terao G, Sakiyama Y, Koizumi S
Department of Pediatrics, Angiogenesis and Vascular Development, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
Blood. 2001 Sep 15;98(6):1882-8. doi: 10.1182/blood.v98.6.1882.
Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.
异常的爱泼斯坦-巴尔病毒（EBV）感染T细胞或自然杀伤细胞在急性EBV相关噬血细胞性淋巴组织细胞增生症（EBV-HLH）和慢性活动性EBV感染（CAEBV）的发病机制中起关键作用。在这些EBV相关疾病中，EBV基因组在淋巴细胞亚群尤其是T细胞亚群中的精确频率和定位尚不清楚。本研究分析了4例急性EBV-HLH患者和4例CAEBV患者循环淋巴细胞亚群中EBV感染细胞的频率。外周血淋巴细胞的EBV编码小RNA-1原位杂交检查显示，EBV-HLH中EBV感染细胞的频率显著更高，分别为1.0%至13.4%，CAEBV中为1.6%至25.6%。急性EBV-HLH和CAEBV之间淋巴细胞亚群中EBV感染的模式有很大不同。在所有EBV-HLH患者中，EBV感染在CD8(+) T细胞中占主导地位，而在CAEBV患者中，主要的EBV感染细胞群体是非CD8(+)淋巴细胞亚群。表型分析显示，来自EBV-HLH和CAEBV的EBV感染细胞群体均被激活。在这两种异常的EBV相关疾病与自限性急性传染性单核细胞增多症之间，潜伏膜蛋白-1、EBV相关核抗原（EBNA）-1和EBNA-2基因的任何EBV亚株均无优势。这些结果表明急性EBV-HLH和CAEBV之间存在不同的病毒-细胞相互作用，提示这两种EBV相关疾病针对EBV感染的致病机制不同，这解释了这两种疾病临床表现的差异。
