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Journal of Virology, March 2006, p. 2445-2452, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2445-2452.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Ataxia-Telangiectasia-Mutated (ATM) Protein Can Enhance Human Immunodeficiency Virus Type 1 Replication by Stimulating Rev Function

Yasuo Ariumi1,2,3 and Didier Trono1,2,4*

Department of Microbiology and Molecular Medicine,1 Frontiers in Genetics National Center for Competence in Research, University of Geneva, Switzerland;,2 Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan,3 School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland4

Received 12 September 2005/ Accepted 12 December 2005

The ataxia-telangiectasia-mutated (ATM) kinase plays a central role in responses to various forms of DNA damage and has been suggested to facilitate human immunodeficiency virus type 1 (HIV-1) integration. Here, we describe a series of experiences that indicate that ATM can enhance HIV-1 replication by stimulating the action of the Rev viral posttranscriptional regulator. The Rev-dependent stimulation of viral late gene expression was observed with ATM-overexpressing cells, a result confirmed with a Rev-dependent reporter construct. Both parameters were also enhanced upon treatment of HeLa cells with caffeine, a xanthine that, in this cellular context, stimulates ATM activity. As well, decreased levels of virions with reduced infectivity were released by ATM knockdown cells. Notably, ATM overexpression did not stimulate the HIV-1 late gene expression within the context of Rev-independent constructs or the Rex-dependent production of capsid from human T-cell leukemia virus type 1 proviral constructs. Altogether, these results indicate that ATM can positively influence HIV-1 Rev function.

* Corresponding author. Mailing address: EPFL SV-DO, Building AAB—Station 15, CH 1015 Lausanne, Switzerland. Phone: 41 21 693 1751. Fax: 41 21 693 1635. E-mail: Didier.trono{at}epfl.ch.

Journal of Virology, March 2006, p. 2445-2452, Vol. 80, No. 5
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.5.2445-2452.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  
  • Ariumi, Y., Kuroki, M., Dansako, H., Abe, K.-I., Ikeda, M., Wakita, T., Kato, N. (2008). The DNA Damage Sensors Ataxia-Telangiectasia Mutated Kinase and Checkpoint Kinase 2 Are Required for Hepatitis C Virus RNA Replication. J. Virol. 82: 9639-9646 [Abstract] [Full Text]  


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