Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming

Scott A. Jones, Daniel N. Clark, Feng Cao, John E. Tavis, Jianming Hu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Hepatitis B virus replicates a DNA genome through reverse transcription of a pregenomic RNA (pgRNA) by using a multifunctional polymerase (HP). A critical function of HP is its specific association with a viral RNA signal, termed ε (Hε), located on pgRNA, which is required for specific packaging of pgRNA into viral nucleocapsids and initiation of viral reverse transcription. HP initiates reverse transcription by using itself as a protein primer (protein priming) and Hε as the obligatory template. HP is made up of four domains, including the terminal protein (TP), the spacer, the reverse transcriptase (RT), and the RNase H domains. A recently developed, Hε-dependent, in vitro protein priming assay was used in this study to demonstrate that almost the entire TP and RT domains and most of the RNase H domain were required for protein priming. Specific residues within TP, RT, and the spacer were identified as being critical for HP-Hε binding and/or protein priming. Comparison of HP sequence requirements for Hε binding, pgRNA packaging, and protein priming allowed the classification of the HP mutants into five groups, each with distinct effects on these complex and related processes. Detailed characterization of HP requirements for these related and essential functions of HP will further elucidate the mechanisms of its multiple functions and aid in the targeting of these functions for antiviral therapy.

Original languageEnglish (US)
Pages (from-to)1564-1572
Number of pages9
JournalJournal of virology
Volume88
Issue number3
DOIs
StatePublished - Feb 1 2014

Fingerprint

RNA-Binding Proteins
Hepatitis B virus
Viral RNA
Product Packaging
RNA
RNA-Directed DNA Polymerase
Proteins
reverse transcription
proteins
RNA-directed DNA polymerase
Reverse Transcription
Ribonuclease H
Nucleocapsid
RNA packaging
nucleocapsid
Antiviral Agents
Carrier Proteins
Genome
taxonomy
DNA

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Jones, Scott A. ; Clark, Daniel N. ; Cao, Feng ; Tavis, John E. ; Hu, Jianming. / Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming. In: Journal of virology. 2014 ; Vol. 88, No. 3. pp. 1564-1572.
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Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming. / Jones, Scott A.; Clark, Daniel N.; Cao, Feng; Tavis, John E.; Hu, Jianming.

In: Journal of virology, Vol. 88, No. 3, 01.02.2014, p. 1564-1572.

Research output: Contribution to journalArticle

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