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Journal of Virology, April 2002, p. 3637-3645, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3637-3645.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Tat Protein of Human Immunodeficiency Virus Type 1 (HIV-1) Can Promote Placement of tRNA Primer onto Viral RNA and Suppress Later DNA Polymerization in HIV-1 Reverse Transcription

Masanori Kameoka,1 Max Morgan,2 Marc Binette,1 Rodney S. Russell,1,2 Liwei Rong,1 Xiaofeng Guo,1 Andrew Mouland,1 Lawrence Kleiman,1 Chen Liang,1 and Mark A. Wainberg1,2*

McGill University AIDS Centre, Lady Davis Institute—Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2,1 Department of Microbiology, McGill University, Montreal, Quebec, Canada H3A 2B42

Received 4 September 2001/ Accepted 11 January 2002

Human immunodeficiency virus type-1 Tat has been proposed to play a role in the regulation of reverse transcription. We previously demonstrated that wild-type Tat can augment viral infectivity by suppressing the reverse transcriptase (RT) reaction at late stages of the viral life cycle in order to prevent the premature synthesis of potentially deleterious viral DNA products. Here we have performed a detailed analysis of the cell-free reverse transcription reaction to elucidate the mechanism(s) whereby Tat can affect this process. Our results show that Tat can suppress nonspecific DNA elongation while moderately affecting the specific initiation stage of reverse transcription. In addition, Tat has an RNA-annealing activity and can promote the placement of tRNA onto viral RNA. This points to a functional homology between Tat and the viral nucleocapsid (NC) protein that is known to be directly involved in this process. Experiments using a series of mutant Tat proteins revealed that the cysteine-rich and core domains of Tat are responsible for suppression of DNA elongation, while each of the cysteine-rich, core, and basic domains, as well as a glutamine-rich region in the C-terminal domain, are important for the placement of tRNA onto the viral RNA genome. These results suggest that Tat can play at least two different roles in the RT reaction, i.e., suppression of DNA polymerization and placement of tRNA onto viral RNA. We believe that the first of these activities of Tat may contribute to the overall efficiency of reverse transcription of the viral genome during a new round of infection as well as to enhanced production of infectious viral particles. We hypothesize that the second activity, illustrating functional homology between Tat and NC, suggests a potential role for NC in the displacement of Tat during viral maturation.

* Corresponding author. Mailing address: McGill University AIDS Centre, Lady Davis Institute—Jewish General Hospital, 3755 Cote-Ste-Catherine Rd., Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7537. E-mail: mark.wainberg{at}mcgill.ca.

Journal of Virology, April 2002, p. 3637-3645, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3637-3645.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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