E2 泛素连接酶 UBE2L6 通过稳定病毒 RNA 聚合酶促进塞内卡病毒 A 的增殖。
E2 ubiquitin-conjugating enzyme UBE2L6 promotes Senecavirus A proliferation by stabilizing the viral RNA polymerase.
机构信息
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
出版信息
PLoS Pathog. 2020 Oct 26;16(10):e1008970. doi: 10.1371/journal.ppat.1008970. eCollection 2020 Oct.
Senecavirus A (SVA), discovered in 2002, is an emerging pathogen of swine that has since been reported in numerous pork producing countries. To date, the mechanism of SVA replication remains poorly understood. In this study, utilizing iTRAQ analysis we found that UBE2L6, an E2 ubiquitin-conjugating enzyme, is up-regulated in SVA-infected BHK-21 cells, and that its overexpression promotes SVA replication. We determined that UBE2L6 interacts with, and ubiquitinates the RNA-dependent RNA polymerase of SVA, (the 3D protein) and this ubiquitination serves to inhibit the degradation of 3D. UBE2L6-mediated ubiquitination of 3D requires a cystine at residue 86 in UBE2L6, and lysines at residues 169 and 321 in 3D. Virus with mutations in 3D (rK169R and rK321R) exhibited significantly decreased replication compared to wild type SVA and the repaired viruses, rK169R(R) and rK321R(R). These data indicate that UBE2L6, the enzyme, targets the 3D polymerase, the substrate, during SVA infection to facilitate replication.
塞尼卡病毒 A（SVA）于 2002 年被发现，是一种新兴的猪病原体，此后在许多猪肉生产国均有报道。迄今为止，SVA 的复制机制仍知之甚少。在这项研究中，我们利用 iTRAQ 分析发现，泛素结合酶 E2L6（UBE2L6）在 SVA 感染的 BHK-21 细胞中上调，并且其过表达促进了 SVA 的复制。我们确定 UBE2L6 与 SVA 的 RNA 依赖性 RNA 聚合酶（3D 蛋白）相互作用，并泛素化该聚合酶，从而抑制其降解。UBE2L6 介导的 3D 泛素化需要 UBE2L6 中残基 86 处的半胱氨酸以及 3D 中残基 169 和 321 处的赖氨酸。与野生型 SVA 和修复病毒 rK169R(R)和 rK321R(R)相比，3D 中具有突变的病毒（rK169R 和 rK321R）的复制明显减少。这些数据表明，UBE2L6 作为一种酶，在 SVA 感染过程中靶向 3D 聚合酶（底物）以促进复制。
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