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Journal of Virology, October 2007, p. 10515-10523, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00947-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vpr Is Required for Efficient Nef Expression from Unintegrated Human Immunodeficiency Virus Type 1 DNA{triangledown}

Betty Poon, Michael A. Chang, and Irvin S. Y. Chen*

Departments of Microbiology, Immunology and Molecular Genetics, and Medicine, David Geffen School of Medicine at UCLA, UCLA AIDS Institute and Jonsson Comprehensive Cancer Center, Los Angeles, California

Received 2 May 2007/ Accepted 13 July 2007

Unintegrated human immunodeficiency virus (HIV) DNA are viral DNA products formed naturally during HIV replication. While the integrated proviral DNA form is transcriptionally active and results in productive infection, unintegrated DNA is also capable of expression of viral RNA and proteins. Previously, we showed that HIV Vpr enhances expression from integrase-defective HIV. Here we show that Vpr activation of expression is partially dependent upon the presence of a transcriptionally active HIV promoter and results in increased transcription of unspliced gag and spliced nef viral RNA. While Tat is detectable during infection with integrase-defective HIV, Tat levels are not affected by the presence of Vpr. Mutation studies reveal that Tat is dispensable for the Vpr-mediated enhancement of expression from unintegrated DNA. We find that virion-associated Vpr is sufficient for Nef expression from unintegrated viral DNA, resulting in the efficient downregulation of CD4 from the surface of infected cells. These results provide a mechanism by which Nef expression from unintegrated HIV type 1 DNA expression occurs.

* Corresponding author. Mailing address: UCLA AIDS Institute, Department of Microbiology, Immunology and Molecular Genetics, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678. Phone: (310) 825-4793. Fax: (310) 267-1875. E-mail: syuchen{at}mednet.ucla.edu

{triangledown} Published ahead of print on 25 July 2007.

Journal of Virology, October 2007, p. 10515-10523, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00947-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Majumder, B., Venkatachari, N. J., O'Leary, S., Ayyavoo, V. (2008). Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells. J. Virol. 82: 7189-7200 [Abstract] [Full Text]  


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