Inhibition of Cellular RNA polymerase II transcription by delta antigen of hepatitis delta virus.
Hepatitis delta virus (HDV) contains a circular, viroid-like RNA and the hepatitis delta antigen (HDAg) protein. The viral RNA is replicated via RNA-dependent RNA synthesis, which is thought to be mediated by host DNA-dependent RNA polymerase II (pol II). The precise mechanism of HDV RNA replication using RNA as a template remains to be elucidated, though it is clear that HDAg is involved. We demonstrate here that both SP1-activated and basal pol II transcription are inhibited by HDAg. This inhibitory effect of HDAg was observed in vivo in transient cotransfection assays as well as in vitro in HeLa nuclear extracts with purified, recombinant HDAg. The in vitro inhibition of pol II transcription could be reversed with excess HeLa nuclear extracts. Furthermore, HDAg specifically inhibited pol II-mediated transcription but not pol I- or III-mediated transcription. These results provide support for the model in which HDAg participates in a complex with host cell pol II transcription factors to mediate pol II-dependent HDV RNA replication, concomitantly cellular pol II transcription.
Howard Hughes Medical Institute, University of Southern California School of Medicine, Los Angeles 90033-1054, USA.
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D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004926:Escherichia coli; D017930:Genes, Reporter; D006367:HeLa Cells; D018963:Hepatitis Antigens / Q000502:physiology*; D003698:Hepatitis Delta Virus / Q000502:physiology*; D035923:Hepatitis delta Antigens; D006801:Humans; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000378:metabolism; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012320:RNA Polymerase III / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic
D018963:Hepatitis Antigens; D035923:Hepatitis delta Antigens; D011994:Recombinant Proteins; C442244:hepatitis delta virus large antigen; D015500:Chloramphenicol O-Acetyltransferase; D012319:RNA Polymerase II; D012318:RNA Polymerase I; D012320:RNA Polymerase III