This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Macnaughton, T. B.
Right arrow Articles by Lai, M. M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Macnaughton, T. B.
Right arrow Articles by Lai, M. M. C.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 3928-3935, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3928-3935.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genomic but Not Antigenomic Hepatitis Delta Virus RNA Is Preferentially Exported from the Nucleus Immediately after Synthesis and Processing

Thomas B. Macnaughton1 and Michael M. C. Lai1,2*

Department of Molecular Microbiology and Immunology,1 Howard Hughes Medical Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033-10542

Received 2 October 2001/ Accepted 4 January 2002

Hepatitis delta virus (HDV) contains a viroid-like circular RNA that replicates via a double rolling circle replication mechanism. It is generally assumed that HDV RNA is synthesized and remains exclusively in the nucleus until being exported to the cytoplasm for virion assembly. Using a [32P]orthophosphate metabolic labeling procedure to study HDV RNA replication (T. B. Macnaughton, S. T. Shi, L. E. Modahl, and M. M. C. Lai. J. Virol. 76:3920-3927, 2002), we unexpectedly found that a significant amount of newly synthesized HDV RNA was detected in the cytoplasm. Surprisingly, Northern blot analysis revealed that the genomic-sense HDV RNA is present almost equally in both the nucleus and cytoplasm, whereas antigenomic HDV RNA was mostly retained in the nucleus, suggesting the specific and highly selective export of genomic HDV RNA. Kinetic studies showed that genomic HDV RNA was exported soon after synthesis. However, only the monomer and, to a lesser extent, the dimer HDV RNAs were exported to the cytoplasm; very little higher-molecular-weight HDV RNA species were detected in the cytoplasm. These results suggest that the cleavage and processing of HDV RNA may facilitate RNA export. The export of genomic HDV RNA was resistant to leptomycin B, indicating that a cell region maintenance 1 (Crm1)-independent pathway was involved. The large form of hepatitis delta antigen (L-HDAg), which is responsible for virus packaging, was not required for RNA export, as a mutant HDV RNA genome unable to synthesize L-HDAg was still exported. The proportions of genomic HDV RNA in the nucleus and cytoplasm remained relatively constant throughout replication, indicating that export of genomic HDV RNA occurred continuously. In contrast, while antigenomic HDV RNA was predominately in the nucleus, there was a proportionally large fraction of antigenomic HDV RNA in the cytoplasm at early time points of RNA replication. These findings uncover a previously unrecognized presence of HDV RNA in the cytoplasm, which may have implications for viral RNA synthesis and packaging.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Ave., Los Angeles, CA 90033-1054. Phone: (323) 442-1748. Fax: (323) 342-9555. E-mail: michlai{at}hsc.usc.edu.

Journal of Virology, April 2002, p. 3928-3935, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3928-3935.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Chang, J., Nie, X., Chang, H. E., Han, Z., Taylor, J. (2008). Transcription of Hepatitis Delta Virus RNA by RNA Polymerase II. J. Virol. 82: 1118-1127 [Abstract] [Full Text]  
  • Li, Y.-J., Macnaughton, T., Gao, L., Lai, M. M. C. (2006). RNA-Templated Replication of Hepatitis Delta Virus: Genomic and Antigenomic RNAs Associate with Different Nuclear Bodies.. J. Virol. 80: 6478-6486 [Abstract] [Full Text]  
  • Chang, J., Nie, X., Gudima, S., Taylor, J. (2006). Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs.. J. Virol. 80: 3205-3214 [Abstract] [Full Text]  
  • Lai, M. M. C. (2005). RNA Replication without RNA-Dependent RNA Polymerase: Surprises from Hepatitis Delta Virus. J. Virol. 79: 7951-7958 [Full Text]  
  • Wang, Y.-H., Chang, S. C., Huang, C., Li, Y.-P., Lee, C.-H., Chang, M.-F. (2005). Novel Nuclear Export Signal-Interacting Protein, NESI, Critical for the Assembly of Hepatitis Delta Virus. J. Virol. 79: 8113-8120 [Abstract] [Full Text]  
  • Li, Y.-J., Stallcup, M. R., Lai, M. M. C. (2004). Hepatitis Delta Virus Antigen Is Methylated at Arginine Residues, and Methylation Regulates Subcellular Localization and RNA Replication. J. Virol. 78: 13325-13334 [Abstract] [Full Text]  
  • Chang, J., Provost, P., Taylor, J. M. (2003). Resistance of Human Hepatitis Delta Virus RNAs to Dicer Activity. J. Virol. 77: 11910-11917 [Abstract] [Full Text]  
  • Qi, Y., Ding, B. (2003). Differential Subnuclear Localization of RNA Strands of Opposite Polarity Derived from an Autonomously Replicating Viroid. Plant Cell 15: 2566-2577 [Abstract] [Full Text]  
  • Chang, J., Taylor, J. M. (2003). Susceptibility of Human Hepatitis Delta Virus RNAs to Small Interfering RNA Action. J. Virol. 77: 9728-9731 [Abstract] [Full Text]  
  • Wong, S. K., Lazinski, D. W. (2002). Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc. Natl. Acad. Sci. USA 99: 15118-15123 [Abstract] [Full Text]  
  • Macnaughton, T. B., Lai, M. M. C. (2002). Large Hepatitis Delta Antigen Is Not a Suppressor of Hepatitis Delta Virus RNA Synthesis once RNA Replication Is Established. J. Virol. 76: 9910-9919 [Abstract] [Full Text]  
  • Macnaughton, T. B., Shi, S. T., Modahl, L. E., Lai, M. M. C. (2002). Rolling Circle Replication of Hepatitis Delta Virus RNA Is Carried Out by Two Different Cellular RNA Polymerases. J. Virol. 76: 3920-3927 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»