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Journal of Virology, October 2001, p. 9087-9095, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9087-9095.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Conserved Serine 177 in the Delta Antigen of Hepatitis Delta Virus Is One Putative Phosphorylation Site and Is Required for Efficient Viral RNA Replication

Jung-Jung Mu,1 Ding-Shinn Chen,2 and Pei-Jer Chen1,2,*

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

Received 2 February 2001/Accepted 9 July 2001

Hepatitis delta virus (HDV) small delta antigen (S-HDAg) plays a critical role in virus replication. We previously demonstrated that the S-HDAg phosphorylation occurs on both serine and threonine residues. However, their biological significance and the exact phosphorylation sites of S-HDAg are still unknown. In this study, phosphorylated S-HDAg was detected only in the intracellular compartment, not in viral particles. In addition, the number of phosphorylated isoforms of S-HDAg significantly increased with the extent of viral replication in transfection system. Site-directed mutagenesis showed that alanine replacement of serine 177, which is conserved among all the known HDV strains, resulted in reduced phosphorylation of S-HDAg, while the mutation of the other two conserved serine residues (2 and 123) had little effect. The S177A mutant dramatically decreased its capability in assisting HDV RNA replication, with a preferential and profound impairment of the antigenomic RNA replication. Furthermore, the viral RNA editing, a step relying upon antigenomic RNA replication, was also abolished by this mutation. These results suggested that phosphorylation of S-HDAg, with serine 177 as a presumable site, plays a critical role in viral RNA replication, especially in augmenting the replication of antigenomic RNA.


* Corresponding author. Mailing address: Graduate Institute of Clinical Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Rd., Taipei, Taiwan. Phone: 88623970800, ext. 7072. Fax: 88623317624. E-mail: peijer{at}ha.mc.ntu.edu.tw.


Journal of Virology, October 2001, p. 9087-9095, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9087-9095.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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Copyright © 2001 by the American Society for Microbiology. All rights reserved.