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Journal of Virology, October 2009, p. 10119-10128, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.02457-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

ADAR1 Interacts with PKR during Human Immunodeficiency Virus Infection of Lymphocytes and Contributes to Viral Replication{triangledown}

Guerline Clerzius,1,2 Jean-François Gélinas,1,3 Aïcha Daher,1 Marion Bonnet,4,{dagger} Eliane F. Meurs,4 and Anne Gatignol1,2,3*

Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research,1 Departments of Experimental Medicine,2 Microbiology & Immunology, McGill University, Montréal, Québec, Canada,3 Department of Virology, Pasteur Institute, Paris, France4

Received 29 November 2008/ Accepted 9 July 2009

The interferon-induced protein kinase RNA activated (PKR) is activated after virus infection. This activation is transient during the human immunodeficiency virus type 1 (HIV-1) infection of lymphocytes, and the protein is not activated at the peak of infection. We observed that interferon-induced adenosine deaminase acting on RNA 1-p150 (ADAR1-p150) and ADAR1-p110 expression increases while the virus replicates actively. Furthermore, both forms of ADAR1 show enhanced interactions with PKR at the peak of HIV infection, suggesting a role for this protein in the regulation of PKR activation. We observed that ADAR1-p150, as previously shown for the TAR RNA binding protein (TRBP), reverses the PKR inhibition of HIV expression and production in HEK 293T cells. This activity requires the Z-DNA binding motif and the three double-stranded RNA binding domains but not the catalytic domain. In astrocytic cells, ADAR1-p150 increased HIV expression and production to an extent similar to that of TRBP. Small interfering RNAs against ADAR1-p150 moderately decreased HIV production. These results indicate that two interferon-induced proteins, ADAR1 and PKR, have antagonistic functions on HIV production. They suggest that ADAR1 and TRBP belong to a multiprotein complex that inhibits PKR during the HIV infection of lymphocytes.

* Corresponding author. Mailing address: Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, 3999 Côte Ste Catherine, Montréal, Quebec H3T1E2, Canada. Phone: (514) 340-8260, ext. 5284. Fax: (514) 340-7576. E-mail: anne.gatignol{at}mcgill.ca

{triangledown} Published ahead of print on 15 July 2009.

{dagger} Present address: Institut für Genetik, Universität zu Köln, Cologne, Germany.

Journal of Virology, October 2009, p. 10119-10128, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.02457-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Toth, A. M., Li, Z., Cattaneo, R., Samuel, C. E. (2009). RNA-specific Adenosine Deaminase ADAR1 Suppresses Measles Virus-induced Apoptosis and Activation of Protein Kinase PKR. J. Biol. Chem. 284: 29350-29356 [Abstract] [Full Text]  


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