Abstract

PML nuclear bodies are cellular structures known to combat DNA viruses. In this study, how human bocavirus 1 (HBoV1), a respiratory pathogen, evades this defense was investigated. PATZ1, a host protein that constitutively regulates gene activity, is recruited by the viral NS1-70 protein to form concentrated clusters adjacent to PML bodies. These clusters bind to the viral DNA and suppress its ability to make new viral genes. To overcome this, the virus produces another protein, NS2, which disrupts the PATZ1 condensates and removes them from the viral DNA, allowing the virus to resume replication. This NS2-mediated antagonism also relieves PATZ1-dependent repression of certain host genes, facilitating viral DNA replication. Beyond HBoV1, PATZ1 also restricts other nuclear-replicating DNA viruses. Our study reveals an intrinsic antiviral mechanism centered on PATZ1-PML condensates and identifies NS2 as a viral antagonist that reprograms host transcription to promote infection.