Porcine circovirus type 2 is the main pathogen of porcine circovirus disease, which has caused enormous economic losses to the pig industry worldwide. The PKR signaling pathway is important for the cellular antiviral response, but its role in the process of PCV2 infection is unknown. In this study, we first found that dsRNA was produced and that PKR was activated in PCV2 infection. However, interestingly, the activation of PKR was inhibited when the Cap protein was exogenously expressed in PAMs, and this inhibition was reversed by the expression of DNAJC7. The interaction between Cap and DNAJC7 was confirmed by laser confocal microscopy, coimmunoprecipitation and GST pull-down, and it was found that PCV2 infection or the expression of Cap protein could induce DNAJC7 to migrate to the nucleus and release P58^IPK, an inhibitor of PKR activation. Downregulating the expression of DNAJC7 by a specific inhibitor or recombinant lentivirus-mediated shRNA, inhibited the replication of the PCV2 genome and the production of virions, which was consistent with the increase of DNAJC7 expression in multiple tissues of weaned piglets infected with PCV2. These data indicate that although PKR was activated by PCV2 infection, the activation was inhibited by Cap through an interaction with DNAJC7. These results help to understand the molecular mechanism of immune escape after PCV2 infection.

2型猪圆环病毒是猪圆环病毒病的主要病原体，已给全世界的养猪业造成了巨大的经济损失。PKR信号通路对于细胞抗病毒反应很重要，但在PCV2感染过程中的作用尚不清楚。在这项研究中，我们首先发现在PCV2感染中产生了dsRNA，并且PKR被激活。然而，有趣的是，当Cap蛋白在PAM中外源表达时，PKR的激活被抑制，而这种抑制被DNAJC7的表达逆转。通过激光共聚焦显微镜，共免疫沉淀和GST下拉证实Cap与DNAJC7之间的相互作用，发现PCV2感染或Cap蛋白的表达可诱导DNAJC7迁移至核并释放P58 ^IPK，是PKR激活的抑制剂。通过特异性抑制剂或重组慢病毒介导的shRNA下调DNAJC7的表达，抑制了PCV2基因组的复制和病毒体的产生，这与在感染了PCV2的断奶仔猪的多个组织中DNAJC7表达的增加是一致的。这些数据表明，尽管PKR被PCV2感染激活，但Cap通过与DNAJC7的相互作用抑制了激活。这些结果有助于了解PCV2感染后免疫逃逸的分子机制。