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Journal of Virology, April 2007, p. 3574-3582, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02569-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immediate Activation Fails To Rescue Efficient Human Immunodeficiency Virus Replication in Quiescent CD4+ T Cells{triangledown}

Dimitrios N. Vatakis,1 Gregory Bristol,1 Thomas A. Wilkinson,2 Samson A. Chow,2,4 and Jerome A. Zack1,3,4*

Division of Hematology and Oncology, Department of Medicine,1 Department of Molecular and Medical Pharmacology,2 Department of Microbiology, Immunology and Molecular Genetics,3 UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 900954

Received 21 November 2006/ Accepted 4 January 2007

Unlike activated T cells, quiescent CD4+ T cells have shown resistance to human immunodeficiency virus (HIV) infection due to a block in the early events of the viral life cycle. To further investigate the nature of this block, we infected quiescent CD4+ T cells with HIV-1NL4-3 and immediately stimulated them. Compared to activated (prestimulated) cells, these poststimulated cells showed slightly decreased viral entry and delays in the completion of reverse transcription. However, the relative efficiency of integration was similar to that of prestimulated cells. Together, this resulted in decreased expression of tat/rev mRNA and synthesis of viral protein. Furthermore, based on cell cycle staining and BrdU incorporation, poststimulated cells expressing viral protein failed to initiate a second round of their cell cycle, independently of Vpr-mediated arrest. Together, these data demonstrate that the early stages of the HIV life cycle are inefficient in these poststimulated cells and that efficient replication cannot be induced by subsequent activation.

* Corresponding author. Mailing address: David Geffen School of Medicine at UCLA, 650 Charles Young Dr. South, Box 951678, 11-934 Factor, Los Angeles, CA 90095-1678. Phone: (310) 825-0876. Fax: (310) 825-6192. E-mail: jzack{at}ucla.edu.

{triangledown} Published ahead of print on 17 January 2007.

Journal of Virology, April 2007, p. 3574-3582, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02569-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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