| Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively prevent virus replication; however, these treatments cannot completely cure HBV infection because of the covalently closed circular DNA. In this study, we identified that tripartite motif-containing protein 26 (TRIM26) is required for efficient HBV replication and characterized its mechanistic function. Small interfering RNA-mediated TRIM26 knockdown (KD) significantly reduced HBV DNA in the culture supernatants of a human primary hepatocyte cell line and HepG2/NTCP cells. Both overexpressed and endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain in HEK293T cells and Huh-7 cells. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ubiquitin ligase. In addition, HBc was degraded by TRIM26 KD, whereas the reduction was restored by a proteasome inhibitor. A RING domain-deleted TRIM26 (TRIM26ΔR) still bound to HBc, but lost the ability to inhibit the HBc ubiquitination. TRIM26ΔR behaved as a dominant negative form of TRIM26 that disturbed the interaction between TRIM26 and HBc and promoted the degradation of HBc. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid proteasome-dependent HBc degradation for efficient replication. The protein-protein interaction between TRIM26 and HBc might be a novel therapeutic target for HBV infection. |
