10th March 2024

•Histone deacetylases (HDAC5) promotes TRIF-mediated IRF3 activation

•HDAC5 restricts multiple orthopoxviruses and is degraded during virus infection

•Orthopoxvirus protein C6 induces HDAC5 degradation

•Protein C6 can bind directly to HDAC5

Below is shown HDAC metabolism

• HDAC5 was shown as degraded during Vaccinia virus (VACV) infection and is a restriction factor for VACV and herpes simplex virus type 1 (HSV1). Regulation of TLRs and IRF3 through HDAC5 may occur.
• The antiviral activity of HDAC5 is antagonized by VACV protein C6 and orthologs from the orthopoxviruses cowpox, rabbitpox, camelpox, monkeypox, and variola. Infection by many of these viruses induces proteasomal degradation of HDAC5, and expression of C6 alone can induce HDAC5 degradation proividing insights into how OPXV proteins regulate IRF3

Further details see:

1. Lu et al: "HDAC5 enhances IRF3 activation and is targeted for degradation by protein C6 from orthopoxviruses including Monkeypox virus and Variola virus"; DOI:https://doi.org/10.1016/j.celrep.2024.113788 

2. Brown et al: "Immunopathogenesis of Orthopoxviridae: insights into immunology from smallpox to monkeypox (mpox)";  https://doi.org/10.37349/ei.2023.00119