Mechanisms of inhibition of nuclear hormone receptor-dependent hepatitis B virus replication by hepatocyte nuclear factor 3beta.
The nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and the retinoid X alpha (RXRalpha) plus the peroxisome proliferator-activated receptor alpha (PPARalpha) heterodimer support hepatitis B virus (HBV) replication in nonhepatoma cells. Hepatocyte nuclear factor 3 (HNF3) inhibits nuclear hormone receptor-mediated viral replication. Inhibition of HBV replication by HNF3beta is associated with the preferential reduction in the level of the pregenomic RNA compared with that of precore RNA. Hepatitis B e antigen (HBeAg), encoded by the precore RNA, mediates part of the inhibition of viral replication by HNF3beta. The amino-terminal transcriptional activation domain of HNF3beta is essential for the inhibition of HBV replication. The activation of transcription by HNF3 from HBV promoters downstream from the nucleocapsid promoter appears to contribute indirectly to the reduction in the steady-state level of 3.5-kb HBV RNA, possibly by interfering with the elongation rate of these transcripts. Therefore, transcriptional interference mediated by HNF3 may also regulate HBV RNA synthesis and viral replication.
Tang
Hong
H
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
McLachlan
Alan
A
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral; D006513:Hepatitis B e Antigens / Q000502:physiology; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051542:Hepatocyte Nuclear Factor 3-beta; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D004268:DNA-Binding Proteins; C496503:Foxa2 protein, mouse; D006513:Hepatitis B e Antigens; D009687:Nuclear Proteins; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta