Inhibition of histone methyltransferase SETD8 represses DNA viruses

Viral infection is one of the most critical threats for human health. Multiple diseases, such as cancer and neural degeneration diseases, are related with the latent infection of DNA viruses. However, it is still difficult to clean up the latent DNA viruses and new anti-viral strategies are important for fighting against the related diseases. Here, we screen a chemical pool and identify a small molecular chemical, UNC0379, as an inhibitor for multiple DNA viruses. UNC0379 is a chemical inhibitor for histone methyltransferase SETD8. SETD8 promotes DNA virus replication and its enzymatic activity is required. Our results further indicated that SETD8 methyltransferase activity is required for PCNA stability, one factor critical for viral DNA replication. Viral infection stimulates the interaction between SETD8 and PCNA and thus enhances PCNA stability and viral DNA replication. Taken together, our study reveals a new mechanism for regulating viral DNA