Mus musculus breed:FVB/N Raw sequence reads. Mus musculus breed:FVB/N

Kaposi Sarcoma (KS) is the most common cancer in AIDS patients and is tightly associated with infection by Kaposi-Sarcoma-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the entire 170,000 bp viral genome induced early-onset, aggressive angiosarcoma (AS) in transgenic mice. The tumors were histopathologically indistinguishable from human KS. Like KS, all tumor cells expressed the viral latency-associated nuclear antigen (LANA). The tumors transcribed most viral genes, whereas endothelial cells in other organs only transcribed the viral latent genes. The tumor cells were of endothelial lineage and exhibited the same molecular pattern of pathway activation as KS, namely PI3K/ Akt /mTOR, IL-10, and VEGF. KSHV-induced AS was more aggressive than Ha-ras-induced AS. Overall survival could be 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 novel therapies, including vaccines.

卡波西肉瘤（Kaposi Sarcoma, KS）是艾滋病患者中最常见的恶性肿瘤，与卡波西肉瘤相关疱疹病毒（Kaposi-Sarcoma-associated herpesvirus, KSHV）感染紧密相关。目前尚无针对卡波西肉瘤的动物模型。将完整的170,000 bp病毒基因组通过原核注射构建转基因小鼠，可诱导其产生早发性侵袭性血管肉瘤（angiosarcoma, AS）。该肿瘤在组织病理学上与人类卡波西肉瘤难以区分。与卡波西肉瘤一致，所有肿瘤细胞均表达病毒潜伏相关核抗原（latency-associated nuclear antigen, LANA）。肿瘤细胞可转录绝大多数病毒基因，而其余器官的内皮细胞仅转录病毒潜伏基因。该肿瘤细胞属于内皮细胞谱系，其通路激活的分子模式与卡波西肉瘤一致，即PI3K/Akt/mTOR、IL-10及VEGF。KSHV诱导的血管肉瘤侵袭性强于Ha-ras诱导的血管肉瘤。预防性使用更昔洛韦（ganciclovir）可提升小鼠的总生存率。综上，全病毒KSHV转基因小鼠是卡波西肉瘤的精准动物模型，为卡波西肉瘤发病机制的遗传学剖析以及包括疫苗在内的新型治疗方案的评估开辟了研究路径。