Nun Tamara K, Kroll David J, Oberlies Nicholas H, Soejarto Djaja D, Case Ryan J, Piskaut Pius, Matainaho Teatulohi, Hilscher Chelsey, Wang Ling, Dittmer Dirk P, Gao Shou-Jian, Damania Blossom
Department of Microbiology and Immunology, Lineberger Cancer Center, University of North Carolina at Chapel Hill, North Carolina, NC 27599, USA.
Mol Cancer Ther. 2007 Aug;6(8):2360-70. doi: 10.1158/1535-7163.MCT-07-0108.
Tumors associated with Kaposi's sarcoma-associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma-associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death.
与卡波西肉瘤相关疱疹病毒感染相关的肿瘤包括卡波西肉瘤、原发性渗出性淋巴瘤和多中心性Castleman病。实际上,这些癌症中的所有肿瘤细胞都受到潜伏感染,并且依赖病毒生存。潜伏病毒蛋白维持病毒基因组,是肿瘤发生所必需的。目前的预防和治疗策略有限,因为它们未能特异性靶向病毒的潜伏形式,而这种形式可在宿主的一生中持续存在。因此,靶向潜伏病毒蛋白可能被证明是治疗现有肿瘤以及通过降低潜伏病毒载量预防肿瘤的重要治疗方式。在此,我们描述了一种基于荧光的新型筛选试验,用于监测B淋巴细胞系中卡波西肉瘤相关疱疹病毒基因组的维持情况,并鉴定诱导其丢失从而导致肿瘤细胞死亡的化合物。