Tumor Virology Program, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
J Clin Invest. 2012 Mar;122(3):1076-81. doi: 10.1172/JCI58530. Epub 2012 Feb 1.
Infections by viruses are associated with approximately 12% of human cancer. Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several malignancies commonly found in AIDS patients. The mechanism of KSHV-induced oncogenesis remains elusive, due in part to the lack of an adequate experimental system for cellular transformation of primary cells. Here, we report efficient infection and cellular transformation of primary rat embryonic metanephric mesenchymal precursor cells (MM cells) by KSHV. Cellular transformation occurred at as early as day 4 after infection and in nearly all infected cells. Transformed cells expressed hallmark vascular endothelial, lymphatic endothelial, and mesenchymal markers and efficiently induced tumors in nude mice. KSHV established latent infection in MM cells, and lytic induction resulted in low levels of detectable infectious virions despite robust expression of lytic genes. Most KSHV-induced tumor cells were in a latent state, although a few showed heterogeneous expression of lytic genes. This efficient system for KSHV cellular transformation of primary cells might facilitate the study of growth deregulation mechanisms resulting from KSHV infections.
病毒感染与大约 12%的人类癌症有关。卡波西肉瘤相关疱疹病毒（KSHV）与艾滋病患者中常见的几种恶性肿瘤有因果关系。由于缺乏适当的原代细胞转化实验系统，KSHV 诱导的致癌机制仍不清楚。在这里，我们报告了 KSHV 对原代大鼠胚胎后肾间充质前体细胞（MM 细胞）的有效感染和细胞转化。细胞转化发生在感染后最早的第 4 天，几乎所有感染的细胞都发生了转化。转化细胞表达了标志性的血管内皮细胞、淋巴管内皮细胞和成纤维细胞标志物，并能有效地在裸鼠中诱导肿瘤。KSHV 在 MM 细胞中建立潜伏感染，尽管裂解基因表达强烈，但裂解诱导后仅检测到低水平的可检测传染性病毒颗粒。大多数 KSHV 诱导的肿瘤细胞处于潜伏状态，尽管少数细胞表现出裂解基因的异质性表达。这种原代细胞的 KSHV 细胞转化的有效系统可能有助于研究 KSHV 感染引起的生长失调机制。
