Division of Animal Infectious Disease, State Key Laboratory of Agricultural Microbiology, HuaZhong Agricultural University, Wuhan, Hubei 430070, PR China.
Virology. 2014 May;456-457:198-204. doi: 10.1016/j.virol.2014.03.028. Epub 2014 Apr 15.
Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases (PCVAD). It has been shown that the ubiquitin-proteasome system (UPS) is correlated with viral infection, but its role in PCV2 replication remains unknown. In the present study, we explored the interplay between PCV2 replication and the UPS in PK15 cells and found that treatment with a proteasome inhibitor (MG132 and lactacystin) significantly decreased the PCV2 titer at the early infection stage. We further revealed that inhibition of the UPS did not affect virus entry but decreased viral protein expression and RNA transcription potentially in a cell cycle-dependent manner. PCV2 infection has little effect on the chymotrypsin-like activity, and the gene-silencing of ubiquitin reduced the PCV2 titer, which indicates that the effective replication of PCV2 may be related to protein ubiquitination. Taken together, our data suggested that PCV2 replication requires the UPS machinery, which may represent a potential antiviral target against PCV2.
猪圆环病毒 2 型（PCV2）是猪圆环病毒相关疾病（PCVAD）的主要病原体。已经表明，泛素-蛋白酶体系统（UPS）与病毒感染相关，但它在 PCV2 复制中的作用尚不清楚。在本研究中，我们在 PK15 细胞中探索了 PCV2 复制与 UPS 之间的相互作用，发现蛋白酶体抑制剂（MG132 和乳胞素）处理在早期感染阶段显著降低了 PCV2 的滴度。我们进一步揭示，UPS 的抑制作用不会影响病毒进入，但可能会以细胞周期依赖性的方式降低病毒蛋白表达和 RNA 转录。PCV2 感染对糜蛋白酶样活性几乎没有影响，泛素基因沉默降低了 PCV2 的滴度，这表明 PCV2 的有效复制可能与蛋白质泛素化有关。综上所述，我们的数据表明，PCV2 的复制需要 UPS 机制，这可能是针对 PCV2 的潜在抗病毒靶点。
