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 Sato, S.
Right arrow Articles by Lazinski, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sato, S.
Right arrow Articles by Lazinski, D. W.

 Previous Article  |  Next Article 

Journal of Virology, August 2004, p. 8120-8134, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8120-8134.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

By Inhibiting Replication, the Large Hepatitis Delta Antigen Can Indirectly Regulate Amber/W Editing and Its Own Expression

Shuji Sato, Cromwell Cornillez-Ty, and David W. Lazinski*

Department of Molecular Biology and Microbiology and the Raymond and Beverly Sackler Research Foundation Laboratory, School of Medicine, Tufts University, Boston, Massachusetts 02111

Received 12 January 2004/ Accepted 30 March 2004

Hepatitis delta virus (HDV) expresses two essential proteins with distinct functions. The small hepatitis delta antigen (HDAg-S) is expressed throughout replication and is needed to promote that process. The large form (HDAg-L) is farnesylated, is expressed only at later times via RNA editing of the amber/W site, and is required for virion assembly. When HDAg-L is artificially expressed at the onset of replication, it strongly inhibits replication. However, there is controversy concerning whether HDAg-L expressed naturally at later times as a consequence of editing and replication can similarly inhibit replication. Here, by stabilizing the predicted secondary structure downstream from the amber/W site, a replication-competent HDV mutant that exhibited levels of editing higher than those of the wild type was created. This mutant expressed elevated levels of HDAg-L early during replication, and at later times, its replication aborted prematurely. No further increase in amber/W editing was observed following the cessation of replication, indicating that editing was coupled to replication. A mutation in HDAg-L and a farnesyl transferase inhibitor were both used to abolish the ability of HDAg-L to inhibit replication. Such treatments rescued the replication defect of the overediting mutant, and even higher levels of amber/W editing resulted. It was concluded that when expressed naturally during replication, HDAg-L is able to inhibit replication and thereby inhibit amber/W editing and its own synthesis. In addition, the structure adjacent to the amber/W site is suboptimal for editing, and this creates a window of time in which replication can occur in the absence of HDAg-L.


* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111-1817. Phone: (617) 636-3671. Fax: (617) 636-0337. E-mail: david.lazinski{at}tufts.edu.


Journal of Virology, August 2004, p. 8120-8134, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8120-8134.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Linnstaedt, S. D., Kasprzak, W. K., Shapiro, B. A., Casey, J. L. (2009). The fraction of RNA that folds into the correct branched secondary structure determines hepatitis delta virus type 3 RNA editing levels. RNA 15: 1177-1187 [Abstract] [Full Text]  
  • Defenbaugh, D. A., Johnson, M., Chen, R., Zheng, Y. Y., Casey, J. L. (2009). Hepatitis Delta Antigen Requires a Minimum Length of the Hepatitis Delta Virus Unbranched Rod RNA Structure for Binding. J. Virol. 83: 4548-4556 [Abstract] [Full Text]  
  • Abrahem, A., Pelchat, M. (2008). Formation of an RNA polymerase II preinitiation complex on an RNA promoter derived from the hepatitis delta virus RNA genome. Nucleic Acids Res 36: 5201-5211 [Abstract] [Full Text]  
  • Linnstaedt, S. D., Kasprzak, W. K., Shapiro, B. A., Casey, J. L. (2006). The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing. RNA 12: 1521-1533 [Abstract] [Full Text]  
  • Jayan, G. C., Casey, J. L. (2005). Effects of Conserved RNA Secondary Structures on Hepatitis Delta Virus Genotype I RNA Editing, Replication, and Virus Production. J. Virol. 79: 11187-11193 [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]  
  • O'Malley, B., Lazinski, D. W. (2005). Roles of Carboxyl-Terminal and Farnesylated Residues in the Functions of the Large Hepatitis Delta Antigen. J. Virol. 79: 1142-1153 [Abstract] [Full Text]