JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01034-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

SUMO modification of small hepatitis delta antigen

Chung-Hsin Tseng, Tai-Shan Cheng, Chiung-Yueh Shu, King-Song Jeng, and Michael M.C. Lai^*

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan; Graduate institute of Microbiology and Graduated Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; UMR 5165, CNRS-Toulouse III University, CHU Purpan, Toulouse, France; Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California, U.S.A.; and National Cheng-Kung University, Tainan, Taiwan

^* To whom correspondence should be addressed. Email: michlai{at}gate.sinica.edu.tw.

Hepatitis delta antigen (HDAg) is a nuclear protein that is intimately involved in hepatitis delta virus (HDV) RNA replication. HDAg consists of two protein species, the small form (S-HDAg) and the large form (L-HDAg). Previous studies have shown that post-translational modifications of S-HDAg, such as phosphorylation, acetylation and methylation, can modulate HDV RNA replication. In this study, we showed that S-HDAg is a small ubiquitin-like modifier-1 (SUMO1) target protein. Mapping data showed that multiple lysine residues are SUMO1 acceptors within S-HDAg. Using a genetic fusion strategy, we found that conjugation of SUMO1 to S-HDAg selectively enhanced HDV genomic RNA and mRNA synthesis but not antigenomic RNA synthesis. This result supports our previous proposition that the cellular machinery involved in the synthesis of HDV antigenomic RNA is different from that of genomic RNA synthesis and mRNA transcription, requiring different modified forms of S-HDAg. Sumoylation represents a new type of modification for the HDAg.