Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs and Key Laboratory of Animal Growth and Development of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Viruses. 2022 Jul 15;14(7):1550. doi: 10.3390/v14071550.
Circoviruses are the smallest single-stranded DNA viruses that infect mammalian species, avian species, fish, and insects. The infections of circoviruses are known to be associated with a series of fatal diseases, but the protease of circovirus still remains unknown. In this research, we identified viral capsid protein (Cap) as the protease of porcine circovirus type 2 (PCV2), to our knowledge the first circoviruses protease to be reported. First, we found that the expression of host proteins is affected due to PCV2 infection in the porcine kidney (PK-15) cells. Then, by proteomic analysis, 253 host proteins that were down regulated were identified due to direct or indirect effects of PCV2. Further, Cap expression, but not other ORFs of PCV2, significantly reduced both JMJD6 (bifunctional arginine demethylase and lysyl-hydroxylase) and CCT5 (the chaperonin containing TCP1 subunit 5) in PK-15 cells. Finally, the results in vitro hydrolysis assays demonstrated that Cap could directly degraded either JMJD6 or CCT5 with different catalytic efficiency. In summary, our study expands repertoire of PCV2 Cap and promotes the development of inhibitors toward the anti-PCV2.
圆环病毒是感染哺乳动物、禽类、鱼类和昆虫的最小的单链 DNA 病毒。已知圆环病毒的感染与一系列致命疾病有关，但圆环病毒的蛋白酶仍然未知。在这项研究中，我们鉴定出猪圆环病毒 2（PCV2）的病毒衣壳蛋白（Cap）为蛋白酶，据我们所知，这是首次报道的圆环病毒蛋白酶。首先，我们发现 PCV2 感染猪肾（PK-15）细胞后，宿主蛋白的表达受到影响。然后，通过蛋白质组学分析，由于 PCV2 的直接或间接影响，鉴定出 253 种下调的宿主蛋白。进一步的，Cap 的表达，而不是 PCV2 的其他 ORFs，在 PK-15 细胞中显著降低了 JMJD6（双功能精氨酸脱甲基酶和赖氨酰羟化酶）和 CCT5（含 TCP1 亚基 5 的伴侣蛋白）。最后，体外水解实验表明 Cap 可以直接降解 JMJD6 或 CCT5，具有不同的催化效率。总之，我们的研究扩展了 PCV2 Cap 的作用谱，并促进了针对抗 PCV2 的抑制剂的开发。
