JVI Accepts, published online ahead of print on 25 July 2007

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J. Virol. doi:10.1128/JVI.00947-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Vpr is required for efficient Nef expression from unintegrated HIV-1 DNA

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

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

^* To whom correspondence should be addressed. Email: syuchen{at}mednet.ucla.edu.

Unintegrated HIV DNA are viral DNA products naturally formed 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. Mutational studies reveal that Tat is dispensable for 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 efficient downregulation of CD4 from the surface of infected cells. These results provide a mechanism by which Nef expression from unintegrated HIV-1 DNA expression occurs.

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