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Journal of Virology, January 2008, p. 692-699, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01155-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Nucleolar Targeting of Hepatitis Delta Antigen Abolishes Its Ability To Initiate Viral Antigenomic RNA Replication{triangledown}

Wen-Hung Huang,1 Yen-Shun Chen,2 and Pei-Jer Chen1,2,3*

Graduate Institute of Clinical Medicine,1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University,2 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan3

Received 28 May 2007/ Accepted 24 October 2007

Hepatitis delta virus (HDV) is a small RNA virus that contains one 1.7-kb single-stranded circular RNA of negative polarity. The HDV particle also contains two isoforms of hepatitis delta antigen (HDAg), small (SHDAg) and large HDAg. SHDAg is required for the replication of HDV, which is presumably carried out by host RNA-dependent RNA polymerases. The localization and the HDAg and host RNA polymerase responsible for HDV replication remain important issues to be addressed. In this study, using recombinant SHDAg fused with a heterologous nucleolar localization sequence (NoLS) to confine its subcellular localization in nucleoli, we aimed to study the effect of SHDAg subcellular localization on HDV RNA replication. The initiation of genomic RNA synthesis from antigenomic template was hardly detectable when SHDAg was fused with the NoLS motif and localized mainly in nucleoli. In contrast, the initiation of antigenomic RNA synthesis was not affected. Drug treatment to release a SHDAg-NoLS mutant from nucleoli could partially restore the replication of HDV genomic RNA from antigenomic RNA. This also recovered the cointeraction between SHDAg and RNA polymerase II. These data strongly suggest that nuclear polymerase (RNA polymerase II) is involved in the synthesis of genomic RNA and that the synthesis of antigenomic RNA can occur in nucleoli. Our results support the idea that the replication of HDV genomic RNA or antigenomic RNA is likely to be carried out by different machineries in different subcellular localizations.

* Corresponding author. Mailing address: Hepatitis Research Center, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan. Phone: 886 2 23123456, ext. 7072. Fax: 886 2 23317624. E-mail: peijerchen{at}ntu.edu.tw

{triangledown} Published ahead of print on 7 November 2007.

Journal of Virology, January 2008, p. 692-699, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01155-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Han, Z., Alves, C., Gudima, S., Taylor, J. (2009). Intracellular Localization of Hepatitis Delta Virus Proteins in the Presence and Absence of Viral RNA Accumulation. J. Virol. 83: 6457-6463 [Abstract] [Full Text]  
  • Chen, Y.-S., Huang, W.-H., Hong, S.-Y., Tsay, Y.-G., Chen, P.-J. (2008). ERK1/2-Mediated Phosphorylation of Small Hepatitis Delta Antigen at Serine 177 Enhances Hepatitis Delta Virus Antigenomic RNA Replication. J. Virol. 82: 9345-9358 [Abstract] [Full Text]  
  • Tseng, C.-H., Jeng, K.-S., Lai, M. M. C. (2008). Transcription of Subgenomic mRNA of Hepatitis Delta Virus Requires a Modified Hepatitis Delta Antigen That Is Distinct from Antigenomic RNA Synthesis. J. Virol. 82: 9409-9416 [Abstract] [Full Text]  
  • Huang, W.-H., Mai, R.-T., Wu Lee, Y.-H. (2008). Transcription Factor YY1 and Its Associated Acetyltransferases CBP and p300 Interact with Hepatitis Delta Antigens and Modulate Hepatitis Delta Virus RNA Replication. J. Virol. 82: 7313-7324 [Abstract] [Full Text]  


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