Li Youwen, Dong Wanyu, Shi Yuejun, Deng Feng, Chen Xi, Wan Chunyun, Zhou Ming, Zhao Ling, Fu Zhen F, Peng Guiqing
The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science, Tarim University, Alar, Xinjiang, China.
The National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Virology. 2016 Jan 15;488:216-24. doi: 10.1016/j.virol.2015.11.018. Epub 2015 Dec 4.
Rabies virus is a highly neurotropic virus that can cause fatal infection of the central nervous system in warm-blooded animals. The RABV phosphoprotein (P), an essential cofactor of the virus RNA-dependent RNA polymerase, is required for virus replication. In this study, the ribosomal protein L9, which has functions in protein translation, is identified as P-interacting cellular factor using phage display analysis. Direct binding between the L9 and P was confirmed by protein pull-down and co-immunoprecipitation analyses. It was further demonstrated that L9 translocates from the nucleus to the cytoplasm, where it colocalizes with P in cells infected with RABV or transfected with P gene. RABV replication was reduced with L9 overexpression and enhanced with L9 knockdown. Thus, we propose that during RABV infection, P binds to L9 that translocates from the nucleus to the cytoplasm, inhibiting the initial stage of RABV transcription.
狂犬病病毒是一种高度嗜神经性病毒，可在温血动物中引起致命的中枢神经系统感染。狂犬病病毒磷蛋白（P）是病毒RNA依赖性RNA聚合酶的必需辅助因子，是病毒复制所必需的。在本研究中，利用噬菌体展示分析，在蛋白质翻译中起作用的核糖体蛋白L9被鉴定为与P相互作用的细胞因子。通过蛋白质下拉和免疫共沉淀分析证实了L9和P之间的直接结合。进一步证明，L9从细胞核转移到细胞质，在感染狂犬病病毒或转染P基因的细胞中，它与P共定位。L9过表达可降低狂犬病病毒复制，而L9敲低则可增强其复制。因此，我们提出，在狂犬病病毒感染期间，P与从细胞核转移到细胞质的L9结合，抑制狂犬病病毒转录的初始阶段。
