Inhibition of histone methyltransferase SETD8 represses DNA virus replication

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 critical for disease treatment. Here, we screen a pool of small chemical molecules and identify UNC0379, an inhibitor for histone H4K20 methyltransferase SETD8, as an effective inhibitor for multiple DNA viruses. UNC0379 not only enhances the expression of anti-viral genes in THP-1 cells, but also repress DNA virus replication in multiple cell lines with defects in cGAS pathway. We prove that SETD8 promotes DNA virus replication in a manner dependent on its enzyme activity. Our results further indicated that SETD8 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 replication and provides a potential strategy for treatment of diseases related with DNA viruses.

 

Comments:

The passage describes a study in which a pool of small chemical molecules was screened to identify potential inhibitors for histone H4K20 methyltransferase SETD8. The researchers found that one particular inhibitor, UNC0379, was effective in inhibiting multiple DNA viruses. They observed that UNC0379 not only increased the expression of anti-viral genes in THP-1 cells but also suppressed DNA virus replication in various cell lines with defects in the cGAS pathway.

The study demonstrated that SETD8, a histone methyltransferase, plays a role in promoting DNA virus replication through its enzymatic activity. The researchers found that SETD8 is necessary for the stability of PCNA (proliferating cell nuclear antigen), a factor critical for viral DNA replication. Upon viral infection, SETD8 interacts with PCNA, leading to enhanced stability of PCNA and increased viral DNA replication.

These findings shed light on a new mechanism for regulating viral DNA replication and provide a potential strategy for treating diseases associated with DNA viruses. By inhibiting SETD8 using UNC0379 or similar inhibitors, it may be possible to interfere with viral replication and potentially mitigate the impact of DNA virus-related diseases such as cancer and neural degeneration diseases.

It is important to note that the passage is a summary of a hypothetical study and not based on any specific real-world scientific research or publication.

Related Products

Cat.No.	Product Name	Information
S7570	UNC0379	UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.3 μM, high selectivity over 15 other methyltransferases.

Related Targets

SETD Histone Methyltransferase