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Journal of Virology, September 2008, p. 9171-9178, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00530-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Functional Analysis of the Complex trans-Activating Response Element RNA Structure in Simian Immunodeficiency Virus{triangledown}

Mireille Centlivre, Bep Klaver, Ben Berkhout, and Atze T. Das*

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 10 March 2008/ Accepted 27 June 2008

Transcription of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is activated through binding of the viral Tat protein to the trans-activating response (TAR) element at the 5' end of the nascent transcript. Whereas HIV type 1 (HIV-1) TAR folds a simple hairpin structure, the corresponding domains of HIV-2 and SIVmac exhibit a more complex structure composed of three stem-loops. This structural polymorphism may be attributed to additional functions of TAR in HIV-2/SIVmac replication. We recently constructed an SIVmac variant that does not require the Tat-TAR interaction for transcription. We used this variant to study additional roles of TAR in SIVmac replication and generated mutants with a truncated TAR structure. We demonstrate that partial or nearly complete removal of TAR does not impair viral transcription, RNA processing, and translation. Moreover, these deletions do not significantly affect virus replication in the PM1 T-cell line and macaque peripheral blood mononuclear cells. These results demonstrate that the complex TAR structure in SIVmac has no other essential function in virus replication in vitro besides its role in Tat-mediated activation of transcription.

* Corresponding author. Mailing address: Laboratory of Experimental Virology, Academic Medical Center, Room K3-115, 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 2 July 2008.

Journal of Virology, September 2008, p. 9171-9178, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00530-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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