Posttranslational Modification of Delta Antigen of Hepatitis D Virus

W.-H. Huang ■ C.-W. Chen ■ H.-L. Wu ■ P.-J. Chen (K)

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan [email protected]

1 Introduction 92

2 The Hypothesis 92

3 IsoprenylationofL-HDAg 93

3.1 Role of L-HDAg Farnesylation in the HDV Replication Cycle 95

3.2 Isoprenylation Enhances the trans-Suppression Activity of L-HDAg 96

3.3 Other Viral Prenylated Proteins 97

4 Phosphorylation of Delta Antigens 97

4.1 Phosphorylated Delta Antigens in the HDV Life Cycle 98

4.2 Putative Delta Antigen Kinase 100

5 Acetylation of Delta Antigen 100

5.1 Enzyme for Delta Antigen Acetylation 101

5.2 Acetylation Site of Delta Antigen 101

5.3 Functions of Delta Antigen Acetylation 102

6 Methylation of Delta Antigen 103

6.1 Enzyme for Delta Antigen Methylation 103

6.2 Methylation Site of Delta Antigen 105

6.3 Functions of Delta Antigen Methylation 105

7 Prospect 106

References 107

Abstract The hepatitis delta virus (HDV) genome has only one open reading frame, which encodes the viral small delta antigen. After RNA editing, the same open reading frame is extended 19 amino acids at the carboxyl terminus and encodes the large delta antigen. These two viral proteins escort the HDV genome through different cellular compartments for the complicated phases of replication, transcription and, eventually, the formation of progeny virions. To orchestrate these events, the delta antigens have to take distinct cues to traffic to the right compartments and make correct molecular contacts. In eukaryotes, post-translational modification (PTM) is a major mechanism of dictating the multiple functions of a single protein. Multiple PTMs, including phosphorylation, isoprenylation, acetylation, and methylation, have been identified on hepatitis delta antigens. In this chapter we review these PTMs and discuss their functions in regulating and coordinating the life cycle of HDV.

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