KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway
KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway
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DOI：
10.1038/sj.onc.1201571
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发表时间：
1997-10-16
期刊：
影响因子：
8
通讯作者：
Moore, PS
中科院分区：
文献类型：
--
作者：
Gao, SJ;Boshoff, C;Moore, PS
卡波西肉瘤相关疱疹病毒（KSHV）是与卡波西肉瘤和罕见的B细胞淋巴瘤（原发性渗出性淋巴瘤）的发展相关的γ疱疹病毒。KSHV基因ORF K9编码vIRF，其是与负责调节细胞内干扰素信号转导的干扰素（IFN）调节因子（IRF）家族的成员具有低但显著同源性的蛋白质（摩尔PS，Boshoff C，韦斯RA和Chang Y.（1996），Science，274，1739-1744），vIRF抑制IPN-β信号转导，如使用与ORI共转染的IFN-应答性ISG 54报道构建体所测量的; K9进入HeLa和293细胞，vIRF还抑制IFN调控下的基因，如通过抑制IFN-β诱导的p21（WAF 1/CIP 1），然而，没有鉴定出IRF阻遏蛋白的直接DNA结合或蛋白质-蛋白质相互作用特征。表达vIRF的稳定转染子NIH 3 T3克隆在软琼脂中和在低血清浓度下生长，在注射到裸鼠中后失去接触抑制并形成肿瘤，表明vIRF具有病毒致癌基因的性质。由于vIRF主要在KSHV感染的B细胞中表达，而不是KS梭形细胞，该研究提示vIRF是在B细胞瘤形成中有活性的转化癌基因，其可为感染细胞提供独特的免疫逃逸机制。该数据与作为宿主细胞抗病毒途径的双重功能的肿瘤抑制途径一致。
Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma, The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996), Science, 274, 1739-1744), vIRF inhibits IPN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORI; K9 into HeLa and 293 cells, vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21(WAF1/CIP1), however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified, Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene, Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells, This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.