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

Margherita Doria, Francesca Neri, Angela Gallo, Maria Giulia Farace, Alessandro Michienzi

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbergkp604
Pages (from-to)5848-5858
Number of pages11
JournalNucleic Acids Research
Volume37
Issue number17
DOIs
Publication statusPublished - Aug 3 2009

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Double-Stranded RNA
RNA Viruses
Virus Diseases
Viruses
Adenosine Deaminase
Adenosine
RNA Editing
T-Lymphocytes
Inosine
5' Untranslated Regions
Gene Expression Regulation
Viral Proteins
Virus Replication
Virion
Genome
Cell Line
Enzymes

ASJC Scopus subject areas

  • Genetics

Cite this

Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. / Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro.

In: Nucleic Acids Research, Vol. 37, No. 17, gkp604, 03.08.2009, p. 5848-5858.

Research output: Contribution to journalArticle

Doria, Margherita ; Neri, Francesca ; Gallo, Angela ; Farace, Maria Giulia ; Michienzi, Alessandro. / Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. In: Nucleic Acids Research. 2009 ; Vol. 37, No. 17. pp. 5848-5858.
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