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

Hepatology. 2009 Aug;50(2):424-33. doi: 10.1002/hep.23011.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Female
  • Gene Expression Regulation, Viral
  • HeLa Cells
  • Hepatitis B virus / physiology*
  • Humans
  • Interferons
  • Mice
  • Mice, Inbred BALB C
  • Minor Histocompatibility Antigens
  • Promoter Regions, Genetic*
  • RING Finger Domains*
  • Repressor Proteins / metabolism*
  • Transfection
  • Tripartite Motif Proteins
  • Viral Core Proteins / metabolism*
  • Virus Replication

Substances

  • Minor Histocompatibility Antigens
  • Repressor Proteins
  • TRIM22 protein, human
  • Tripartite Motif Proteins
  • Viral Core Proteins
  • Interferons