Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

Nucleic Acids Res. 2009 Sep;37(17):5848-58. doi: 10.1093/nar/gkp604. Epub 2009 Aug 3.


Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4(+) T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5' untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / metabolism*
  • CD4-Positive T-Lymphocytes / enzymology
  • Cell Line
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Human Immunodeficiency Virus Proteins / metabolism
  • Humans
  • Jurkat Cells
  • RNA Editing*
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins
  • Virion / metabolism


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