Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC-host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti-MVC approach.

中文翻译：

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伴侣分子 Hsc70 和 Hsp70 在犬科动物博卡细小病毒微小病毒的复制中发挥不同的作用

犬微小病毒 (MVC) 属于细小病毒科的博卡细小病毒属（以前称为博卡病毒），会在全世界的新生犬科动物中引起严重的呼吸道和胃肠道症状。有效的病毒感染依赖于病毒生命周期各个阶段宿主因子的成功招募。然而，人们对 MVC 与宿主细胞相互作用知之甚少。在这项研究中，我们发现两种细胞蛋白（Hsc70 和 Hsp70）与 MVC 的 NS1 和 VP2 蛋白相互作用，并且 Hsc70/Hsp70 的两个结构域都介导它们的相互作用。功能研究表明，Hsp70是由MVC感染诱导的，Hsc70的敲低显着抑制了MVC的复制，而Hsp70敲低则显着促进了复制。有趣的是，少量过度表达的 Hsp70 增强了病毒蛋白表达和病毒产量，但大量 Hsp70 过度表达却削弱了它们。 Hsp70过表达后，我们观察到病毒蛋白的泛素化随着Hsp70过表达而改变，蛋白酶体抑制剂（MG132）恢复了病毒蛋白的积累。此外，我们验证了 Hsp70 家族抑制剂显着降低了 MVC 复制。总体而言，我们确定 Hsc70 和 Hsp70 是 MVC NS1 和 VP2 蛋白的相互作用蛋白，并参与 MVC 复制，这可能为抗 MVC 方法提供新的靶点。