Nucleic Acids Research Advance Access originally published online on August 3, 2009
Nucleic Acids Research 2009 37(17):5848-5858; doi:10.1093/nar/gkp604
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Nucleic Acids Research, 2009, Vol. 37, No. 17 5848-5858
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection
1Laboratory of Immunoinfectivology, 2RNA editing Laboratory, Children's Hospital Bambino Gesù, 00165 and 3Department of Experimental Medicine and Biochemical Sciences, University of Rome ‘Tor Vergata’, 00133, Rome, Italy
*To whom correspondence should be addressed. Tel: +39 06 72596054; Fax: +39 06 72596053; Email: a_michienzi{at}yahoo.com
Correspondence may also be addressed to Margherita Doria. Tel: +39 06 72596823; Fax: +39 06 72596822; Email: doria{at}uniroma2.it
Correspondence may also be addressed to Angela Gallo. Tel: +39 06 68592658; Fax: +39 06 68592904; Email: gallo{at}opbg.net
Received April 2, 2009. Revised July 1, 2009. Accepted July 2, 2009.
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.