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Roles of Interferon Lambda on Hepatitis B Virus Replication

Other Title
B형 간염 바이러스의 감염과 관련된 인터페론 람다 시스템의 역할과 조절
Authors
홍, 승호
Degree
Doctor (2006)
Abstract
"Background/Aims: Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-α (IFN-α) and the nucleosidic inhibitors of the viral polymerase, lamivudine and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and by the substantial resistance of the virus to nucleosidic inhibitors. New antiviral molecules suitable for monotherapy or combination therapy are highly desired. Recently described IFN-λ family utilizing its distinct cellular receptor has been reported to exert inhibitory effect on replication of several viruses. In this study, I wanted to know whether IFN-λ1 inhibits HBV replication in human hepatoma cell lines and whether HBV modulates expression of CRF2-12, a subunit of IFN-λ1 receptor. In addition, I wanted to establish ELISA for IFN-λ1 to examine HBV mediated modulation of IFN-λ1 production. Methods: I produced IFN-λ1 using E.coli expression system. For antiviral activity of IFN-λ1, I used a functional form of MBP-IFN-λ1 and for generation of antibody against IFN-λ1, I used His-IFN-λ1. I analyzed HBV replication in WT10 and PEB8 human hepatoma cell lines supporting HBV replication, after treatment of these cells with IFN-λ1 by real-time PCR and Southern blotting. After treatment of PEB8 with IFN-λ1, I examined the transcription level of HBV by Northern blotting and the amount of secretory viral Ag by ELISA. I performed the RT-PCR to investigate the induction of antiviral proteins, MxA and 2’5’-OAS, by IFN-λ1. I investigated the expression of CRF2-12 by RT-PCR and Western blotting. I generated monoclonal Abs against IFN-λ1 using splenocytes from immunized mice and determined the detection limit of ELISA using these Abs. Results: HBV replication in PEB8 but not in WT10 was suppressed by IFN-λ1 treatment. In both cell lines, similar amount of CRF2-12 to that in their parental cell line was expressed, and similar amount of transcripts of MxA as well as 2’5’-OAS were induced by IFN-λ1. In PEB8, neither HBV transcripts nor secretory Ag was affected by IFN-λ1 treatment. IFN-λ1 was detected by ELISA using monoclonal Abs and polyclonal Ab generated in this study with the detection limit of 40 ng/ml. Conclusions: Antiviral activity of IFN-λ1 on HBV was demonstrated in one of two human hepatoma cell lines suggesting that the effect of IFN-λ1 may be dependent on the cellular factors, and/or viral factors. My results showed that CRF2-12 expression was not regulated by HBV replication. Finally, an assay for IFN-λ1 production was established. "
Keywords
Hepatitis B VirusIFN-lambda-1 proteinVirus replications
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Theses > School of Medicine / Graduate School of Medicine > Doctor
AJOU Authors
홍승호
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