Hyperediting of Human T-cell Leukemia Virus Type 2 and Simian T-cell Leukemia Virus Type 3 by the dsRNA Adenosine Deaminase ADAR-1

J Gen Virol. 2012 Dec;93(Pt 12):2646-2651. doi: 10.1099/vir.0.045146-0. Epub 2012 Sep 19.

Abstract

RNA editing mediated by adenosine deaminases acting on RNA (ADARs) converts adenosine (A) to inosine (I) residues in dsRNA templates. While ADAR-1-mediated editing was essentially described for RNA viruses, the present work addresses the issue for two δ-retroviruses, human T-cell leukemia virus type 2 and simian T-cell leukemia virus type 3 (HTLV-2 and STLV-3). We examined whether ADAR-1 could edit HTLV-2 and STLV-3 virus genomes in cell culture and in vivo. Using a highly sensitive PCR-based method, referred to as 3DI-PCR, we showed that ADAR-1 could hypermutate adenosine residues in HTLV-2. STLV-3 hypermutation was obtained without using 3DI-PCR, suggesting a higher mutation frequency for this virus. Detailed analysis of the dinucleotide editing context showed preferences for 5' ArA and 5' UrA. In conclusion, the present observations demonstrate that ADAR-1 massively edits HTLV-2 and STLV-3 retroviruses in vitro, but probably remains a rare phenomenon in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / chemistry
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Animals
  • Base Sequence
  • Genome, Viral
  • HEK293 Cells
  • Human T-lymphotropic virus 2 / genetics*
  • Human T-lymphotropic virus 2 / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction / methods
  • RNA Editing / physiology*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins
  • Sequence Homology, Nucleic Acid
  • Simian T-lymphotropic virus 3 / genetics*
  • Simian T-lymphotropic virus 3 / metabolism*

Substances

  • RNA, Viral
  • RNA-Binding Proteins
  • ADARB1 protein, human
  • Adenosine Deaminase
  • Adenosine