Figure 5.

Model of the role of HDAC6 in TRIM21-mediated ADIN. TRIM21 senses the entry of antibody-bound AdVs and recruits HDAC6, which deacetylates and promotes the dimerization of TRIM21 via the coiled-coil domain. TRIM21 homodimers bind AdV-antibody complexes via the Fc domain of the antibody and target the complexes to the proteasome for degradation through automonoubiquitination and subsequent polyubiquitination. In the absence of HDAC6, TRIM21 is hyperacetylated, which inhibits the formation of TRIM21 homodimers; antibody-bound AdVs fail to be removed through TRIM21-mediated ADIN, resulting in viral replication and expression of viral proteins.