Flore O, Rafii S, Ely S, O'Leary J J, Hyjek E M, Cesarman E
Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
Nature. 1998 Aug 6;394(6693):588-92. doi: 10.1038/29093.
Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is invariably present in Kaposi's sarcoma lesions. KSHV contains several viral oncogenes and serological evidence suggests that KSHV infection is necessary for the development of Kaposi's sarcoma, but cellular transformation by this virus has not so far been demonstrated. KSHV is found in the microvascular endothelial cells in Kaposi's sarcoma lesions and in the spindle 'tumour' cells, which are also thought to be of endothelial origin. Here we investigate the biological consequences of infecting human primary endothelial cells with purified KSHV particles. We find that infection causes long-term proliferation and survival of these cells, which are associated with the acquisition of telomerase activity and anchorage-independent growth. KSHV was present in only a subset of cells, and paracrine mechanisms were found to be responsible for the survival of uninfected cells. Their survival may have been mediated by upregulation of a receptor for vascular endothelial growth factor. Our results indicate that transformation of endothelial cells by KSHV, as well as paracrine mechanisms that are induced by this virus, may be critical in the pathogenesis of Kaposi's sarcoma.
卡波西肉瘤相关疱疹病毒（KSHV），即人类疱疹病毒8型，始终存在于卡波西肉瘤病变中。KSHV含有多种病毒癌基因，血清学证据表明KSHV感染是卡波西肉瘤发生所必需的，但迄今为止，这种病毒导致的细胞转化尚未得到证实。在卡波西肉瘤病变的微血管内皮细胞以及纺锤形“肿瘤”细胞中发现了KSHV，这些纺锤形“肿瘤”细胞也被认为起源于内皮细胞。在此，我们研究了用纯化的KSHV颗粒感染人原代内皮细胞的生物学后果。我们发现感染导致这些细胞长期增殖和存活，这与端粒酶活性的获得和不依赖贴壁生长有关。KSHV仅存在于一部分细胞中，并且发现旁分泌机制负责未感染细胞的存活。它们的存活可能是由血管内皮生长因子受体的上调介导的。我们的结果表明，KSHV对内皮细胞的转化以及这种病毒诱导的旁分泌机制，可能在卡波西肉瘤的发病机制中起关键作用。
