Zhu Guoliang, Xi Fei, Zeng Wuxia, Zhao Yifei, Cao Weijun, Liu Chen, Yang Fan, Ru Yi, Xiao Shuqi, Zhang Shilei, Liu Huanan, Tian Hong, Yang Fayu, Lu Biao, Sun Shukai, Song Haiyang, Sun Bozhang, Zhao Xiaoyi, Tang Lijie, Li Kangli, He Jijun, Guo Jianhong, Zhu Yun, Zhu Zixiang, Sun Fei, Zheng Haixue
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
African Swine Fever Regional Laboratory of China, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Nat Commun. 2025 Jan 8;16(1):501. doi: 10.1038/s41467-024-55683-z.
African swine fever virus is highly contagious and causes a fatal infectious disease in pigs, resulting in a significant global impact on pork supply. The African swine fever virus RNA polymerase serves as a crucial multifunctional protein complex responsible for genome transcription and regulation. Therefore, it is essential to investigate its structural and functional characteristics for the prevention and control of African swine fever. Here, we determine the structures of endogenous African swine fever virus RNA polymerase in both nucleic acid-free and elongation states. The African swine fever virus RNA polymerase shares similarities with the core of typical RNA polymerases, but possesses a distinct subunit M1249L. Notably, the dynamic binding mode of M1249L with RNA polymerase, along with the C-terminal tail insertion of M1249L in the active center of DNA-RNA scaffold binding, suggests the potential of M1249L to regulate RNA polymerase activity within cells. These results are important for understanding the transcription cycle of the African swine fever virus and for developing antiviral strategies.
非洲猪瘟病毒具有高度传染性，可导致猪的致命传染病，对全球猪肉供应产生重大影响。非洲猪瘟病毒RNA聚合酶是一种关键的多功能蛋白复合物，负责基因组转录和调控。因此，研究其结构和功能特性对于预防和控制非洲猪瘟至关重要。在此，我们确定了无核酸状态和延伸状态下内源性非洲猪瘟病毒RNA聚合酶的结构。非洲猪瘟病毒RNA聚合酶与典型RNA聚合酶的核心有相似之处，但拥有一个独特的亚基M1249L。值得注意的是，M1249L与RNA聚合酶的动态结合模式，以及M1249L的C末端尾巴插入DNA-RNA支架结合活性中心，表明M1249L在细胞内调节RNA聚合酶活性的潜力。这些结果对于理解非洲猪瘟病毒的转录周期和制定抗病毒策略具有重要意义。
