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 journalArticle

18 Citations (Scopus)

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

Fingerprint

Viral RNA
Reverse Transcription
Binding Sites
RNA
DNA
Duck Hepatitis B Viruses
Nucleotide Motifs
RNA-Directed DNA Polymerase
Hepatitis B virus
Antiviral Agents
Epitopes
Ligands
Antibodies

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Badtke, Matthew P. ; Khan, Irfan ; Cao, Feng ; Hu, Jianming ; Tavis, John E. / An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription. In: Virology. 2009 ; Vol. 390, No. 1. pp. 130-138.
@article{a24313433c954f42a53dd24f86ac3ec6,
title = "An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription",
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.",
author = "Badtke, {Matthew P.} and Irfan Khan and Feng Cao and Jianming Hu and Tavis, {John E.}",
year = "2009",
month = "7",
day = "20",
doi = "10.1016/j.virol.2009.04.023",
language = "English (US)",
volume = "390",
pages = "130--138",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription. / Badtke, Matthew P.; Khan, Irfan; Cao, Feng; Hu, Jianming; Tavis, John E.

In: Virology, Vol. 390, No. 1, 20.07.2009, p. 130-138.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An interdomain RNA binding site on the hepadnaviral polymerase that is essential for reverse transcription

AU - Badtke, Matthew P.

AU - Khan, Irfan

AU - Cao, Feng

AU - Hu, Jianming

AU - Tavis, John E.

PY - 2009/7/20

Y1 - 2009/7/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67649479264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649479264&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2009.04.023

DO - 10.1016/j.virol.2009.04.023

M3 - Article

C2 - 19467554

AN - SCOPUS:67649479264

VL - 390

SP - 130

EP - 138

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -