An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription

Matthew P. Badtke, Irfan Khan, Feng Cao, Jianming Hu, John E. Tavis

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The T3 motif on the duck hepatitis B virus reverse transcriptase (P) is proposed to be a binding site essential for viral replication, but its ligand and roles in DNA synthesis are unknown. Here, we found that T3 is needed for P to bind the viral RNA, the first step in DNA synthesis. A second motif, RT-1, was predicted to assist T3. T3 and RT-1 appear to form a composite RNA binding site because mutating T3 and RT-1 had similar effects on RNA binding, exposure of antibody epitopes on P, and DNA synthesis. The T3 and RT-1 motifs bound RNA non-specifically, yet they were essential for specific interactions between P and the viral RNA. This implies that specificity for the viral RNA is provided by a post-binding step. The T3:RT-1 motifs are conserved with the human hepatitis B virus and may be an attractive target for novel antiviral drug development.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalVirology
Volume390
Issue number1
DOIs
StatePublished - Jul 20 2009

All Science Journal Classification (ASJC) codes

  • Virology

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