Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses, and is degraded via vaccinia virus protein C6
Lu Y., Stuart JH., Talbot-Cooper C., Agrawal-Singh S., Huntly B., Smid AI., Snowden JS., Dupont L., Smith GL.
Significance Histone deacetylases (HDACs) are regulators of host gene expression. HDAC4 is shown here to have an important role in type I interferon (IFN) signaling. Here, multiple cell lines lacking HDAC4 had impaired responses to IFN-α and were rescued by reintroduction of HDAC4. The biological significance of HDAC4 was demonstrated by the enhanced replication and spread of two DNA viruses, vaccinia virus (VACV) and herpes simplex virus type I, in HDAC4 −/− cells, and their diminished replication when HDAC4 was overexpressed. Furthermore, HDAC4 was targeted for proteasomal degradation early after infection with VACV, and VACV protein C6, an inhibitor of type I IFN signaling, was necessary and sufficient for this degradation. In summary, HDAC4 is a restriction factor for large DNA viruses.