Department of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
J Cell Biochem. 2010 May;110(1):1-9. doi: 10.1002/jcb.22524.
Tumor viruses can induce cell transformation by overcoming cellular defense mechanisms and promoting the ungoverned proliferation of infected cells. To this end, functionally related viral oncogenes have evolved in disparate viruses to over-ride key proliferative and survival intracellular pathways, thus assuring efficient viral replication and contributing to tumor formation. Indeed, the study of viral oncogenes has been a powerful tool for disclosing fundamental insights into these basic cellular processes. In this regard, the Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8), the etiological agent of Kaposi's sarcoma (KS), is an exemplary model of an oncogenic virus that includes within its genome several homologues of cellular genes implicated in the regulation of cell proliferation and apoptosis. However, emerging evidence now points to a single KSHV gene, ORF74, encoding for the viral G protein-coupled receptor (vGPCR), as essential for KS development. Expressed in only a fraction of cells within KS lesions, this viral receptor induces tumorigenesis through both autocrine and paracrine mechanisms. Indeed, work from several laboratories has demonstrated that vGPCR can promote cell proliferation, enhance cell survival, modulate cell migration, stimulate angiogenesis, and recruit inflammatory cells, both in expressing cells, as well as in neighboring (bystander) cells. Examination of this powerful viral oncogene may expose novel targets for the treatment of patients with KS and could ultimately provide a unique perspective into how GPCRs, and specifically chemokine receptors, contribute to angiogenesis and tumorigenesis.
肿瘤病毒可以通过克服细胞防御机制和促进感染细胞的不受控制增殖来诱导细胞转化。为此，不同病毒中进化出了功能相关的病毒癌基因，以克服关键的增殖和存活细胞内途径，从而确保有效的病毒复制并促进肿瘤形成。事实上，对病毒癌基因的研究一直是揭示这些基本细胞过程的基本原理的有力工具。在这方面，卡波济肉瘤相关疱疹病毒（KSHV 或 HHV8）是卡波济肉瘤（KS）的病原体，是一种包含几个参与细胞增殖和凋亡调节的细胞基因同源物的致癌病毒的典范模型。然而，新出现的证据现在指向 KSHV 基因 ORF74，其编码病毒 G 蛋白偶联受体（vGPCR），是 KS 发展所必需的。该病毒受体仅在 KS 病变中的一部分细胞中表达，通过自分泌和旁分泌机制诱导肿瘤发生。事实上，来自几个实验室的工作表明，vGPCR 可以促进细胞增殖、增强细胞存活、调节细胞迁移、刺激血管生成和招募炎症细胞，无论是在表达细胞中，还是在相邻（旁观者）细胞中。对这种强大的病毒癌基因的研究可能会揭示出治疗 KS 患者的新靶点，并最终为 GPCR 特别是趋化因子受体如何促进血管生成和肿瘤发生提供独特的视角。
