The hepatitis B virus polymerase

Daniel N. Clark, Razia Tajwar, Jianming Hu, John E. Tavis

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Hepatitis B virus (HBV) is a hepatotropic, partially double-stranded DNA virus that replicates by reverse transcription and is a major cause of chronic liver disease and hepatocellular carcinoma. Reverse transcription is catalyzed by the four-domain multifunctional HBV polymerase (P) protein that has protein-priming, RNA- and DNA-dependent DNA synthesis (i.e., reverse transcriptase), and ribonuclease H activities. P also likely promotes the three strand transfers that occur during reverse transcription, and it may participate in immune evasion by HBV. Reverse transcription is primed by a tyrosine residue in the amino-terminal domain of P, and P remains covalently attached to the product DNA throughout reverse transcription. The reverse transcriptase activity of P is the target for the nucleos(t)ide analog drugs that dominate HBV treatment, and P is the target of ongoing efforts to develop new drugs against both the reverse transcriptase and ribonuclease H activities. Despite the unusual reverse transcription pathway catalyzed by P and the importance of P to HBV therapy, understanding the enzymology and structure of HBV P severely lags that of the retroviral reverse transcriptases due to substantial technical challenges to studying the enzyme. Obtaining a better understanding of P will broaden our appreciation of the diversity among reverse transcribing elements in nature, and will help improve treatment for people chronically infected with HBV.

Original languageEnglish (US)
Title of host publicationViral Replication Enzymes and their Inhibitors Part B
EditorsCraig E. Cameron, Jamie J. Arnold, Laurie S. Kaguni
PublisherAcademic Press
Pages195-226
Number of pages32
ISBN (Print)9780323900164
DOIs
StatePublished - Jan 2021

Publication series

NameEnzymes
Volume50
ISSN (Print)1874-6047

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Biochemistry
  • Molecular Biology

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