Guyot D J, Newbound G C, Lairmore M D
Center for Retrovirus Research and Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210-1093, USA.
Virology. 1997 Jul 21;234(1):123-9. doi: 10.1006/viro.1997.8636.
Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of adult T cell leukemia/lymphoma and several chronic progressive immune-mediated diseases. Approximately 1-4% of infected individuals develop disease, generally decades following infection. Increased proviral transcription, mediated by the viral 40-kDa trans-activating protein, Tax, has been implicated in the pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains sequences responsive to cyclic AMP and protein kinase C, we hypothesized that lymphocyte activation signals initiated through the TCR/CD3 complex or CD2 receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate that mAbs directed against the CD2, but not the CD3 receptor increase viral p24 capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an immortalized HTLV-1 cell line. Consistent with transcriptional regulation, reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene construct under control of the HTLV-1 promoter. These data suggest a possible physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte activation may promote viral transcription in infected lymphocytes.
人类嗜T淋巴细胞病毒1型（HTLV-1）被认为是成人T细胞白血病/淋巴瘤以及几种慢性进行性免疫介导疾病的病原体。大约1%-4%的感染者会发病，通常在感染数十年后。由病毒40 kDa反式激活蛋白Tax介导的原病毒转录增加与HTLV-1相关疾病的发病机制有关。由于HTLV-1启动子包含对环磷酸腺苷和蛋白激酶C有反应的序列，我们推测通过TCR/CD3复合物或CD2受体启动的淋巴细胞激活信号会促进HTLV-1感染的淋巴细胞中的病毒复制。我们证明，针对CD2而非CD3受体的单克隆抗体可使CD2/CD3+ HTLV-1感染的细胞培养上清液中的病毒p24衣壳蛋白增加1.5至5.7倍。Northern印迹分析表明，在永生化的HTLV-1细胞系OSP2/4细胞的CD2交联后，所有种类的病毒mRNA增加2.5至4倍。与转录调控一致，在用表达Tax的质粒和受HTLV-1启动子控制的CAT报告基因构建体共转染的CD2刺激的Jurkat T细胞中，报告基因活性增加了约11倍。这些数据提示了一种可能的生理机制，即CD2介导的细胞黏附和淋巴细胞激活可能促进感染淋巴细胞中的病毒转录。
