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Mol Cell Biol, April 1998, p. 1919-1926, Vol. 18, No. 4
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Hepatitis Delta Virus RNA Editing Is Highly Specific for the Amber/W Site and Is Suppressed by Hepatitis Delta Antigen

Andrew G. Polson,1,dagger Herbert L. Ley III,1 Brenda L. Bass,1 and John L. Casey2,*

Department of Biochemistry and Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84132,1 and Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 208522

Received 27 October 1997/Returned for modification 10 December 1997/Accepted 24 December 1997

RNA editing at adenosine 1012 (amber/W site) in the antigenomic RNA of hepatitis delta virus (HDV) allows two essential forms of the viral protein, hepatitis delta antigen (HDAg), to be synthesized from a single open reading frame. Editing at the amber/W site is thought to be catalyzed by one of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). In vitro, the enzymes ADAR1 and ADAR2 deaminate adenosines within many different sequences of base-paired RNA. Since promiscuous deamination could compromise the viability of HDV, we wondered if additional deamination events occurred within the highly base paired HDV RNA. By sequencing cDNAs derived from HDV RNA from transfected Huh-7 cells, we determined that the RNA was not extensively modified at other adenosines. Approximately 0.16 to 0.32 adenosines were modified per antigenome during 6 to 13 days posttransfection. Interestingly, all observed non-amber/W adenosine modifications, which occurred mostly at positions that are highly conserved among naturally occurring HDV isolates, were found in RNAs that were also modified at the amber/W site. Such coordinate modification likely limits potential deleterious effects of promiscuous editing. Neither viral replication nor HDAg was required for the highly specific editing observed in cells. However, HDAg was found to suppress editing at the amber/W site when expressed at levels similar to those found during HDV replication. These data suggest HDAg may regulate amber/W site editing during virus replication.

* Corresponding author. Mailing address: Division of Molecular Virology and Immunology, Georgetown University Medical Center, 5640 Fishers Lane, Rockville, MD 20852. Phone: (301) 881-2676. Fax: (301) 881-0810. E-mail: caseyj{at}medlib.georgetown.edu.

dagger Present address: Department of Microbiology, University of San Francisco Medical Center, San Francisco, CA 94143-0414.




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