TIMM29 interacts with hepatitis B virus preS1 to modulate the HBV life cycle

概要

〔目的(Purpose)〕
　Hepatitis B virus (HBV), a major global health problem, can cause chronic hepatitis, liver ciirhosis and hepatocellular carcinomas in chronically infected patients. However, before HBV infection can be adequately controlled, many mysteries about the HBV life cycle must be solved.

〔方法ならびに成績(Methods/Results)〕
　In this study, we identified TIMM29, an inner mitochondrial membrane protein, as an interaction partner of the preSl region of the HBV large S protein. The interaction was verified by both an immunoprecipitation with preS 1 peptides and a GST-pulldown assay. Immunofluorescence studies also showed colocalization of preS 1 and TIMM29. Moreover, we determined that the preSl bound with amino acids 92-189 of the T1MM29 protein. Infection of HBV in TIMM29-overexpressing NTCP/G2 cells resulted in a significant decrease of HBeAg and both extracellular particle-associated and core particle-associated HBV DNA without affecting cccDNA formation. Comparable results were obtained with TIMM29-Overexpressing HB611 cells, which constitutively produce HBV. In contrast, knockout of TIMM29 in NTCP/G2 cells led to higher production of HBV including HBeAg expression, as did knockout of T1MM29 in HB611.

〔総括(Conclusion)〕
　Collectively, these results suggested that TIMM29 interacts with the preS 1 region of the HBV large S protein and modulates HBV amplification.