Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes
Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes
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DOI：
10.1016/s1535-6108(02)00237-4
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发表时间：
2003-01-01
期刊：
影响因子：
50.3
通讯作者：
Gutkind, JS
中科院分区：
文献类型：
--
作者：
Montaner, S;Sodhi, A;Gutkind, JS
卡波西肉瘤疱疹病毒 (KSHV) 已被确定为卡波西肉瘤 (KS) 的病原体，但导致 KS 发展的初始事件仍不清楚。 KSHV 基因组的表征揭示了许多潜在癌基因的存在。为了解决它们对内皮细胞衍生的 KS 肿瘤起始的贡献，我们开发了一种新型转基因小鼠，使用表达候选 KSHV 癌基因的病毒实现体内内皮细胞特异性感染。在这里，我们表明，vGPCR 基因的转导足以诱导与人类 KS 极其相似的血管增殖性肿瘤。表达vGPCR的内皮细胞能够通过表达KSHV潜伏基因的细胞进一步促进肿瘤形成，这表明病毒基因在促进卡波西肉瘤发生中发挥协同作用。
The Kaposi's sarcoma herpesvirus (KSHV) has been identified as the etiologic agent of Kaposi's sarcoma (KS), but initial events leading to KS development remain unclear. Characterization of the KSHV genome reveals the presence of numerous potential oncogenes. To address their contribution to the initiation of the endothelial cell-derived KS tumor, we developed a novel transgenic mouse that enabled endothelial cell-specific infection in vivo using virus expressing candidate KSHV oncogenes. Here we show that transduction of one gene, vGPCR, was sufficient to induce angioproliferative tumors that strikingly resembled human KS. Endothelial cells expressing vGPCR were further able to promote tumor formation by cells expressing KSHV latent genes, suggestive of a cooperative role among viral genes in the promotion of Kaposi's sarcomagenesis.