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Journal of Virology, July 2007, p. 7742-7748, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00392-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The TAR Hairpin of Human Immunodeficiency Virus Type 1 Can Be Deleted When Not Required for Tat-Mediated Activation of Transcription{triangledown}

Atze T. Das,* Alex Harwig, Martine M. Vrolijk, and Ben Berkhout

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands

Received 23 February 2007/ Accepted 2 May 2007

The human immunodeficiency virus type 1 (HIV-1) RNA genome contains a terminal repeat (R) region that encodes the transacting responsive (TAR) hairpin, which is essential for Tat-mediated activation of gene expression. TAR has also been implicated in several other processes during viral replication, including translation, dimerization, packaging, and reverse transcription. However, most studies in which replication of TAR-mutated viruses was analyzed were complicated by the dominant negative effect of the mutations on transcription. We therefore used an HIV-1 variant that does not require TAR for transcription to reinvestigate the role of TAR in HIV-1 replication. We demonstrate that this virus can replicate efficiently upon complete deletion of TAR. Furthermore, evolution of a TAR-deleted variant in long-term cultures indicates that HIV-1 requires a stable stem-loop structure at the start of the viral transcripts in which the 5'-terminal nucleotides are base paired. This prerequisite for efficient replication can be fulfilled by the TAR hairpin but also by unrelated stem-loop structures. We therefore conclude that TAR has no essential function in HIV-1 replication other than to accommodate Tat-mediated activation of transcription.

* Corresponding author. Mailing address: Laboratory of Experimental Virology, Academic Medical Center, room K3-106, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: (31-20) 566 3396. Fax: (31-20) 691 6531. E-mail: a.t.das{at}amc.uva.nl

{triangledown} Published ahead of print on 9 May 2007.

Journal of Virology, July 2007, p. 7742-7748, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00392-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Centlivre, M., Klaver, B., Berkhout, B., Das, A. T. (2008). Functional Analysis of the Complex trans-Activating Response Element RNA Structure in Simian Immunodeficiency Virus. J. Virol. 82: 9171-9178 [Abstract] [Full Text]  
  • Vrolijk, M. M., Ooms, M., Harwig, A., Das, A. T., Berkhout, B. (2008). Destabilization of the TAR hairpin affects the structure and function of the HIV-1 leader RNA. Nucleic Acids Res 36: 4352-4363 [Abstract] [Full Text]  
  • Das, A. T., Klaver, B., Harwig, A., Vink, M., Ooms, M., Centlivre, M., Berkhout, B. (2007). Construction of a Doxycycline-Dependent Simian Immunodeficiency Virus Reveals a Nontranscriptional Function of Tat in Viral Replication. J. Virol. 81: 11159-11169 [Abstract] [Full Text]  


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