PATZ1 Condensation Adjacent to PML Nuclear Bodies Suppresses HBoV Transcription as an Intrinsic Antiviral Defense

PML nuclear bodies (PML NBs) are membraneless nuclear compartments that contribute to intrinsic immune defenses against DNA viruses. Here, we identify the host transcription factor PATZ1 as a novel antiviral effector that forms condensates adjacent to PML NBs to suppress human bocavirus 1 (HBoV1) transcription. The viral protein NS1-70, which is essential for HBoV1 DNA replication, triggers the phase separation of PATZ1 into condensates near PML NBs. These condensates act as an intrinsic antiviral defense by recruiting PATZ1 to G-rich regions of the viral genome, thereby repressing viral RNA transcription. To counter this restriction, the alternatively spliced viral protein NS2 interacts with PATZ1, disrupting both PATZ1 condensate formation and its association with the viral genome. Furthermore, PATZ1 also binds G-rich motifs within host gene loci, and NS2-mediated disruption of PATZ1 condensates similarly alleviates transcriptional repression of host genes, thereby facilitating viral replication. Beyond HBoV1, PATZ1 also restricts additional DNA viruses including minute virus of canines (MVC), human parvovirus B19, hepatitis B virus (HBV) and human papillomavirus (HPV), highlighting a conserved antiviral role. Collectively, our findings reveal an unrecognized intrinsic antiviral mechanism involving PATZ1–PML NBs interactions and identify NS2 as a viral antagonist that reprograms host transcription to promote productive infection.