Tripartite Motif-Containing 22 Inhibits the Activity of Hepatitis B Virus Core Promoter, Which Is Dependent on Nuclear-Located RING Domain
Author(s): Gao B (Gao, Bo)1, Duan ZJ (Duan, Zhijian)1, Xu W (Xu, Wei)1, Xiong SD (Xiong, Sidong)1,2
Source: HEPATOLOGY Volume: 50 Issue: 2 Pages: 424-433 Published: AUG 2009
Times Cited: 0 References: 33 Citation Map
Abstract: Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed. that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. Conclusion: These findings suggest that TRIM22, which exhibits anti-HBV activity by acting as a transcriptional suppressor, may play an important role in the clearance of HBV. (HEPATOLOGY 2009;50:424-433.)