Hdv Rna Replication Ancient Relic or Primer

department of Molecular Microbiology and Immunology, Keck School of Medicine,

University of Southern California, Los Angeles, CA 90033, USA

2Institute of Molecular Biology, Academia Sinica, Nankang, 115 Taipei, Taiwan

[email protected]

1 Introduction 25

2 Hepatitis Delta Virus Background 26

2.1 Structure of HDV and HDV RNA 27

2.2 HDAg 28

3 The HDV Replication Cycle 30

3.1 Transcription and Replication 33

3.2 The Role of HDAg in HDV RNA Replication 34

3.3 Replication of Genomic vs. Antigenomic RNA:

Differences and Similarities 36

3.4 Mechanism of Transcription and Replication 37

4 Perspectives 40

References 41

Abstract HDV replicates its circular RNA genome using a double rolling-circle mechanism and transcribes a hepatitis delta antigen-encodeing mRNA from the same RNA template during its life cycle. Both processes are carried out by RNA-dependent RNA synthesis despite the fact that HDV does not encode an RNA-dependent RNA polymerase (RdRP). Cellular RNA polymerase II has long been implicated in these processes. Recent findings, however, have shown that the syntheses of genomic and antigenomic RNA strands have different metabolic requirements, including sensitives to a-amanitin and the site of synthesis. Evidence is summarized here for the involvement of other cellular polymerases, probably pol I, in the synthesis of antige-nomic RNA strand. The ability of mammalian cells to replicate HDV RNA implies that RNA-dependent RNA synthesis was preserved throughout evolution.

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