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Journal of Virology, July 2003, p. 7786-7795, Vol. 77, No. 14
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.14.7786-7795.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Differential Inhibition of RNA Editing in Hepatitis Delta Virus Genotype III by the Short and Long Forms of Hepatitis Delta Antigen
Qiufang Cheng, Geetha C. Jayan, and John L. Casey*
Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, D.C. 20007-2197
Received 9 January 2003/
Accepted 17 April 2003
Hepatitis delta virus (HDV) produces two essential forms of the sole viral protein from the same open reading frame by using host RNA editing activity at the amber/W site in the antigenomic RNA. The roles of these two forms, HDAg-S and HDAg-L, are opposed. HDAg-S is required for viral RNA replication, whereas HDAg-L, which is produced as a result of editing, inhibits viral RNA replication and is required for virion packaging. Both the rate and amount of editing are important because excessive editing will inhibit viral RNA replication, whereas insufficient editing will reduce virus secretion. Here we show that for HDV genotype III, which is associated with severe HDV disease, HDAg-L strongly inhibits editing of a nonreplicating genotype III reporter RNA, while HDAg-S inhibits only when expressed at much higher levels. The different inhibitory efficiencies are due to RNA structural elements located ca. 25 bp 3' of the editing site in the double-hairpin RNA structure required for editing at the amber/W site in HDV genotype III RNA. These results are consistent with regulation of amber/W editing in HDV genotype III by a negative-feedback mechanism due to differential interactions between structural elements in the HDV genotype III RNA and the two forms of HDAg.
* Corresponding author. Mailing address: Department of Microbiology and Immunology, Georgetown University Medical Center, 3900 Reservoir Rd., N.W., Washington, DC 20007. Phone: (202) 687-1052. Fax: (202) 687-1800. E-mail:
caseyj{at}georgetown.edu.
Journal of Virology, July 2003, p. 7786-7795, Vol. 77, No. 14
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.14.7786-7795.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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