Rodriguez-Frandsen Ariel, de Lucas Susana, Pérez-González Alicia, Pérez-Cidoncha Maite, Roldan-Gomendio Alejandro, Pazo Alejandra, Marcos-Villar Laura, Landeras-Bueno Sara, Ortín Juan, Nieto Amelia
Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Ciber de Enfermedades Respiratorias, ISCIII, Spain.
Sci Rep. 2016 Feb 11;6:20744. doi: 10.1038/srep20744.
The influenza A virus polymerase associates with a number of cellular transcription-related factors, including the RNA polymerase II (RNAP II). We previously described that the cellular protein hCLE/C14orf166 interacts with and stimulates influenza virus polymerase as well as RNAP II activities. Here we show that, despite the considerable cellular shut-off observed in infected cells, which includes RNAP II degradation, hCLE protein levels increase throughout infection in a virus replication-dependent manner. Human and avian influenza viruses of various subtypes increase hCLE levels, but other RNA or DNA viruses do not. hCLE colocalises and interacts with viral ribonucleoproteins (vRNP) in the nucleus, as well as in the cytoplasm late in infection. Furthermore, biochemical analysis of purified virus particles and immunoelectron microscopy of infected cells show hCLE in virions, in close association with viral vRNP. These findings indicate that hCLE, a cellular protein important for viral replication, is one of the very few examples of transcription factors that are incorporated into particles of an RNA-containing virus.
甲型流感病毒聚合酶与多种细胞转录相关因子相互作用，包括RNA聚合酶II（RNAP II）。我们之前描述过，细胞蛋白hCLE/C14orf166与流感病毒聚合酶相互作用并刺激其活性，同时也刺激RNAP II的活性。在此我们表明，尽管在感染细胞中观察到明显的细胞功能关闭，包括RNAP II降解，但hCLE蛋白水平在整个感染过程中以病毒复制依赖的方式增加。各种亚型的人流感病毒和禽流感病毒都会增加hCLE水平，但其他RNA或DNA病毒则不会。hCLE在细胞核中与病毒核糖核蛋白（vRNP）共定位并相互作用，在感染后期也在细胞质中如此。此外，对纯化病毒颗粒的生化分析以及对感染细胞的免疫电子显微镜观察显示，hCLE存在于病毒粒子中，与病毒vRNP紧密结合。这些发现表明，hCLE作为一种对病毒复制很重要的细胞蛋白，是极少数被纳入含RNA病毒颗粒的转录因子之一。
