PDF(Pubmed)
Abstract：
Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.
摘要：
卡波西肉瘤（KS）是HIV感染者中最常见的癌症。它是由KS相关疱疹病毒（KSHV）引起的。不存在KS的动物模型。170,000bp病毒基因组的核注射诱导早期发作，转基因小鼠的侵袭性血管肉瘤。肿瘤在组织病理学上与人KS没有区别。就像人类KS一样，所有肿瘤细胞都表达病毒潜伏期相关核抗原（LANA）。肿瘤转录大多数病毒基因，而其他器官中的内皮细胞只转录病毒潜伏基因。肿瘤细胞具有内皮谱系，并表现出与KS相同的途径激活的分子模式，即磷脂酰肌醇3-激酶（PI3K）/Akt/mTOR，白细胞介素-10（IL-10），血管内皮生长因子(VEGF)。KSHV诱导的肿瘤比Ha-ras诱导的血管肉瘤更具侵袭性。预防性更昔洛韦增加了总生存率。因此，全病毒KSHV转基因小鼠代表了KS的准确模型，并为KS发病机理的遗传解剖和治疗评估打开了大门。包括疫苗。
