The NS1 Protein of the Parvovirus MVM Aids in the Localization of the Viral Genome to Cellular Sites of DNA Damage

The autonomous parvovirus Minute Virus of Mice (MVM) localizes to cellular sites of DNA damage to establish viral replication centers, visualized by focal depositions of the essential MVM phosphoprotein NS1. However, how such foci are established remains unknown. Here, we show that MVM NS1 localized to cellular sites of DNA damage independently of its known ability to covalently bind the viral genome at its known consensus DNA binding site. NS1 that retained its capacity to bind its cognate DNA binding sequence could relocate either the viral genome, or heterologous DNA, containing those sites, to cellular sites of DNA damage. These findings suggest that another way that NS1 can facilitate virus infection is by localizing the genome to cellular sites which contain replication and expression proteins. Overall design: Examination of MVM non-structural protein NS1 binding to cellular sites relative to sites of DNA damage during ectopic expression in mouse cells.

自主复制型细小病毒小鼠细小病毒（Minute Virus of Mice, MVM）可定位于细胞DNA损伤位点以构建病毒复制中心，这一过程可通过MVM必需磷酸蛋白NS1的局灶沉积被可视化。然而，此类局灶结构的形成机制至今仍未明确。本研究证实，MVM编码的NS1可独立于其已知的、可在保守DNA结合位点与病毒基因组发生共价结合的能力，定位于细胞DNA损伤位点。保留同源DNA结合序列结合能力的NS1，可将携带此类结合位点的病毒基因组或异源DNA招募至细胞DNA损伤位点。上述研究结果表明，NS1可通过将病毒基因组定位于含有复制与表达蛋白的细胞微环境，以此促进病毒感染，这是NS1介导病毒感染的另一途径。实验整体设计：在小鼠细胞中进行异位表达实验，分析MVM非结构蛋白NS1与细胞DNA损伤位点相对应的细胞结合位点的结合情况。