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Journal of Virology, November 2008, p. 10864-10872, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00238-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Double-Stranded RNA Adenosine Deaminases Enhance Expression of Human Immunodeficiency Virus Type 1 Proteins{triangledown}

Angsana Phuphuakrat,1 Romchat Kraiwong,2 Chompunuch Boonarkart,1 Darat Lauhakirti,1 Tun-Hou Lee,3 and Prasert Auewarakul1*

Department of Microbiology,1 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,2 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts3

Received 2 February 2008/ Accepted 19 August 2008

ADARs (adenosine deaminases that act on double-stranded RNA) are RNA editing enzymes that catalyze a change from adenosine to inosine, which is then recognized as guanosine by translational machinery. We demonstrate here that overexpression of ADARs but not of an ADAR mutant lacking editing activity could upregulate human immunodeficiency virus type 1 (HIV-1) structural protein expression and viral production. Knockdown of ADAR1 by RNA silencing inhibited HIV-1 production. Viral RNA harvested from transfected ADAR1-knocked-down cells showed a decrease in the level of unspliced RNA transcripts. Overexpression of ADAR1 induced editing at a specific site in the env gene, and a mutant with the edited sequence was expressed more efficiently than the wild-type viral genome. These data suggested the role of ADAR in modulation of HIV-1 replication. Our data demonstrate a novel mechanism in which HIV-1 employs host RNA modification machinery for posttranscriptional regulation of viral protein expression.

* Corresponding author. Mailing address: Department of Microbiology, Faculty of Medicine Siriraj Hospital, 2 Prannok Road, Bangkok Noi, Bangkok 10700, Thailand. Phone: 662 4197068. Fax: 662 4184148. E-mail: sipaw{at}mahidol.ac.th

{triangledown} Published ahead of print on 27 August 2008.

Journal of Virology, November 2008, p. 10864-10872, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00238-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Clerzius, G., Gelinas, J.-F., Daher, A., Bonnet, M., Meurs, E. F., Gatignol, A. (2009). ADAR1 Interacts with PKR during Human Immunodeficiency Virus Infection of Lymphocytes and Contributes to Viral Replication. J. Virol. 83: 10119-10128 [Abstract] [Full Text]  
  • Doria, M., Neri, F., Gallo, A., Farace, M. G., Michienzi, A. (2009). Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. Nucleic Acids Res 37: 5848-5858 [Abstract] [Full Text]  


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