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. Examination of MVM non-structural protein NS1 binding to cellular sites relative to sites of DNA damage during ectopic expression in mouse cells.