Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death
Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death
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DOI：
10.1128/jvi.76.17.8797-8807.2002
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发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
Choe, J
中科院分区：
文献类型：
--
作者：
Seo, T;Lee, D;Choe, J
卡波西肉瘤相关疱疹病毒（KSHV）在卡波西肉瘤、原发性渗出性淋巴瘤和某些形式的多中心Castleman病的发展中起着重要作用。KSHV开放阅读框K9编码病毒干扰素（IFN）因子1（vIRF 1），其下调IFN和IRF介导的转录激活，并导致啮齿动物成纤维细胞的细胞转化和裸鼠肿瘤的诱导。使用酵母双杂交试验，我们确定了与类维生素A干扰素诱导的死亡率-19（GRIM 19）相关的基因，该基因在体内和体外均与vIRF 1直接相互作用。vIRF 1的N-末端区域是结合GRIM 19所必需的。在293 T细胞中观察到vIRF 1和GRIM 19的共定位。vIRF 1蛋白在IFN/全反式维甲酸（RA）存在下下调GRIM 19诱导的细胞凋亡，并抑制IFN/RA诱导的细胞死亡。另一种DNA肿瘤病毒蛋白，人乳头瘤病毒16型E6，也结合GRIM 19，表明这是病毒蛋白的一般靶点。我们的研究结果共同表明，vIRF 1通过与GRIM 19相互作用调节IFN/RA细胞死亡信号。
Kaposi's sarcoma-associated herpesvirus (KSHV) plays a significant role in the development of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The KSHV open reading frame K9 encodes the viral interferon (IFN) factor 1 (vIRF1), which downregulates IFN- and IRF-mediated transcriptional activation, and leads to cellular transformation in rodent fibroblasts and induction of tumors in nude mice. Using the yeast two-hybrid assay, we identified genes associated with retinoid-IFN-induced mortality-19 (GRIM19), which interacts directly with vIRF1, both in vivo and in vitro. The N-terminal region of vIRF1 is required for binding GRIM19. Colocalization of vIRF1 and GRIM19 was observed in 293T cells. The vIRF1 protein deregulates GRIM19-induced apoptosis in the presence of IFN/all-trans-retinoic acid (RA) and inhibits IFN/RA-induced cell death. Another DNA tumor viral protein, human papillomavirus type 16 E6, also binds GRIM19, suggesting that this is a general target of viral proteins. Our results collectively indicate that vIRF1 modulates IFN/RA-cell death signals via interactions with GRIM19.