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Development of a fluorescence-based assay to screen antiviral drugs against Kaposis sarcoma– associated herpesvirus

机译:基于荧光的检测方法的开发以筛选抗卡波西氏肉瘤相关疱疹病毒的抗病毒药物

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摘要

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.
机译:与卡波济氏肉瘤相关的疱疹病毒感染相关的肿瘤包括卡波济氏肉瘤,原发性渗出性淋巴瘤和多中心Castleman病。实际上,这些癌症中的所有肿瘤细胞都被潜在感染,并依赖病毒生存。潜在的病毒蛋白维持病毒基因组,是肿瘤发生所必需的。当前的预防和治疗策略受到限制,因为它们无法专门针对病毒的潜伏形式,而这种潜伏形式可以持续到宿主的整个生命周期。因此,靶向潜伏病毒蛋白可能被证明是现有肿瘤的重要治疗方式,并且通过减少潜伏病毒载量在预防肿瘤中也被证明是重要的治疗手段。在这里,我们描述了一种新型的基于荧光的筛选测定法,以监测B淋巴细胞细胞系中卡波西氏肉瘤相关疱疹病毒基因组的维持情况,并确定诱导其丢失并导致肿瘤细胞死亡的化合物。

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