Internal ribosome entry site regulates translation of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein
Internal ribosome entry site regulates translation of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein
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DOI：
10.1128/jvi.75.6.2938-2945.2001
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发表时间：
2001-03-01
影响因子：
5.4
通讯作者：
Collins, M
中科院分区：
文献类型：
--
作者：
Low, W;Harries, M;Collins, M
γ疱疹病毒卡波西肉瘤相关疱疹病毒（KSHV）（或人类疱疹病毒8）与免疫功能低下个体的内皮肿瘤卡波西肉瘤（KS）和淋巴组织增生性疾病相关。只有少量的病毒蛋白表达在B细胞潜伏感染KSHV，在这里，我们的特点，其中之一，病毒FLICE抑制蛋白V-FLIP（K13，ORF 71）的表达机制。v-FLIP编码区存在于双顺反子信息中，在v-cyclin编码区之后。使用体外翻译和细胞转染试验，我们已经确定了一个内部核糖体进入位点（IRES）之前的V-FLIP起始密码子和重叠的v-细胞周期蛋白（ORF 72）编码区，这使得V-FLIP翻译。使用针对v-FLIP的抗体，我们检测到内源性蛋白在潜伏感染的KSHV阳性原发性渗出性淋巴瘤（PEL）细胞系中的表达。通过从PEL细胞中抽取血清诱导细胞凋亡导致V-FLIP合成相对增加，如先前对于从IRES翻译的一些细胞蛋白所述。
The gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) is associated with the endothelial tumor Kaposi's sarcoma (KS) and lymphoproliferative disorders in immunocompromised individuals. Only a small number of viral proteins are expressed in B cells latently infected with KSHV; here we characterize the mechanism of expression of one of these, the viral FLICE inhibitory protein V-FLIP (K13, ORF71). The v-FLIP coding region is present in a bicistronic message, following the v-cyclin coding region. Using both in vitro translation and cell transfection assays, we have identified an internal ribosome entry site (IRES) preceding the V-FLIP start codon and overlapping the v-cyclin (ORF 72) coding region, which allows v-FLIP translation. Using an antibody against v-FLIP we have detected expression of the endogenous protein in latently infected KSHV-positive primary effusion lymphoma (PEL) cell lines. Induction of apoptosis by serum withdrawal from PEL cells results in a relative increase in V-FLIP synthesis, as previously described for some cellular proteins translated from IRES.