Hijacking of host PCNA by circovirus replication-associated protein to recruit POLD1 drives viral DNA replication and is inhibited by R428.

Circoviruses hijack host PCNA to recruit POLD1, driving viral DNA replication, which can be inhibited by the drug R428, offering a potential treatment strategy.

• Why it matters: Understanding how circoviruses exploit host cellular machinery is crucial for developing targeted therapies against these viruses, especially given their impact on animals and potential zoonotic risk.
• What they did: The study identified that circovirus Rep proteins bind to host PCNA via conserved motifs, recruiting POLD1 to viral replication centers, with POLD1 being the main polymerase for viral DNA synthesis; R428 was screened to block this interaction.
• The result: Blocking the Rep-PCNA interaction with R428 significantly suppressed circovirus replication and reduced tissue damage in animal models, highlighting a promising approach for controlling circovirus infections.