Roles of hepatocyte nuclear factors in hepatitis B virus infection.
Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB.
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim, Department of Pharmacology, and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 143-701, South Korea.
Doo Hyun
DH
Kim
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim, Department of Pharmacology, and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 143-701, South Korea.
Hong Seok
HS
Kang
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim, Department of Pharmacology, and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 143-701, South Korea.
Kyun-Hwan
KH
Kim
D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D004270:DNA, Circular / Q000502:physiology; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000209:etiology*; D051536:Hepatocyte Nuclear Factors / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004270:DNA, Circular; D051536:Hepatocyte Nuclear Factors; D035683:MicroRNAs; D014157:Transcription Factors
Covalently closed circular DNA; Hepatitis B virus; Hepatocyte nuclear factor; Replication