Affiliation:
1. Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University
2. the First Affiliated Hospital of Chongqing Medical University
Abstract
Abstract
Background
Hepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide.The triple motif protein 38 (TRIM38) is an interferon-stimulated gene (ISG) that can indirectly inhibit various DNA and RNA viruses by modulating the type I interferon response.However, the relationship between TRIM38 and HBV infection and therapy is yet to be elucidated.Our study aims to investigate the correlation between TRIM38 expression levels and the efficacy of HBV infection and IFN-α therapy in patients with CHB.
Methods
TRIM38 was overexpressed or knocked down in human hepatoma cells and the cells and supernatant were collected.The levels of HBV RNA, pgRNA and supernatant antigen were detected by qRT-PCR or ELISA to evaluate the inhibitory effect of TRIM38 on HBV.Blood samples of CHB patients who received pegylated interferon-α(PEG-IFN-α) therapy were collected, and PBMC was isolated.The alternation in the gene expression level of TRIM38 was detected by qRT-PCR, and the predictive value of TRIM38 changes during early therapy was evaluated.The induction of antiviral proteins was analyzed by immunoblotting.
Results
In human hepatoma cells, TRIM38 was highly induced by IFN-alpha (IFN-α) and enhanced anti-HBV activity.Furthermore, combined treatment with TRIM38 and IFN-α increased antiviral proteins levels.The overexpression of TRIM38 inhibited while knockdown of TRIM38 elevated HBV replication and gene expression in HepG2 and HepG2.2.15 cells.TRIM38 is negatively correlated with chronic HBV infection.Prospective study showed that high levels of TRIM38 in peripheral blood PBMCs were observed in the early responders, and higher TRIM38 expression co-related with a better response to PEG-IFN-α therapy.
Conclusions
Taken together, our study suggested that TRIM38 plays a vital role in HBV replication and gene expression and TRIM38 may become a new target for the treatment of HBV.
Publisher
Research Square Platform LLC