Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain.
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.


CONCLUSIONS
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.
Gao
Bo
B
Department of Immunology, Institute for Immunobiology, Shanghai Medical College of Fudan University, People's Republic of China.
Duan
Zhijian
Z
Xu
Wei
W
Xiong
Sidong
S
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D007372:Interferons; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D011401:Promoter Regions, Genetic; D054829:RING Finger Domains; D012097:Repressor Proteins / Q000378:metabolism*; D014162:Transfection; D000070584:Tripartite Motif Proteins; D014758:Viral Core Proteins / Q000378:metabolism*; D014779:Virus Replication
D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D014758:Viral Core Proteins; D007372:Interferons