Cha Seho, Choe Joonho, Seo Taegun
Department of Life Science, Dongguk University-Seoul, Goyang 10326, South Korea.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea.
Biochem Biophys Res Commun. 2016 Oct 28;479(4):697-702. doi: 10.1016/j.bbrc.2016.09.150. Epub 2016 Sep 28.
Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of Kaposi's sarcoma and primary effusion lymphoma. Like other herpesviruses, KSHV has two distinct life cycles: latent and lytic. Among KSHV latent genes, viral interferon regulatory factor 3 (vIRF3), which shares homology with cellular IRFs, is a multifunctional protein. To identify unknown functions of vIRF3, we performed luciferase-reporter assays in the presence of vIRF3. These analyses revealed that overexpression of vIRF3 inhibited T-cell factor (TCF)-dependent transcriptional activity. This TCF-dependent transcription was associated with the Wnt signaling pathway, which normally regulates embryonic development, but contributes to oncogenesis under dysregulated conditions. Using a mutagenesis analysis, we identified a CREB-binding protein-interaction motif (LXXLL) in vIRF3 as an important region for its inhibitory activity. Collectively, our findings provide insight into the dysregulation of host signaling pathways in KSHV-infected cells.
卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤和原发性渗出性淋巴瘤的病原体。与其他疱疹病毒一样，KSHV有两种不同的生命周期：潜伏和裂解。在KSHV潜伏基因中，与细胞IRF具有同源性的病毒干扰素调节因子3（vIRF3）是一种多功能蛋白。为了确定vIRF3的未知功能，我们在有vIRF3存在的情况下进行了荧光素酶报告基因检测。这些分析表明，vIRF3的过表达抑制了T细胞因子（TCF）依赖性转录活性。这种TCF依赖性转录与Wnt信号通路有关，Wnt信号通路通常调节胚胎发育，但在失调的情况下会促进肿瘤发生。通过诱变分析，我们确定vIRF3中的一个CREB结合蛋白相互作用基序（LXXLL）是其抑制活性的重要区域。总的来说，我们的研究结果为深入了解KSHV感染细胞中宿主信号通路的失调提供了依据。
