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Journal of Virology, June 2000, p. 5639-5646, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Human Immunodeficiency Virus Type 1 TAR RNA Upper Stem-Loop Plays Distinct Roles in Reverse Transcription and RNA Packagingdagger

David Harrich,* C. William Hooker, and Emma Parry

HIV Research Unit, National Centre for HIV Virology Research, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Queensland, Australia 4029

Received 27 January 2000/Accepted 7 March 2000

The human immunodeficiency virus type 1 (HIV-1) RNA genome is flanked by a repeated sequence (R) that is required for HIV-1 replication. The first 57 nucleotides of R form a stable stem-loop structure called the transactivation response element (TAR) that can interact with the virally encoded transcription activator protein, Tat, to promote high levels of gene expression. Recently, we demonstrated that TAR is also important for efficient HIV-1 reverse transcription, since HIV-1 mutated in the upper stem-loop of TAR showed a reduced ability both to initiate and to complete reverse transcription. We have analyzed a series of HIV-1 mutant viruses to better defined the structural or sequence elements required for natural endogenous reverse transcription and packaging of virion RNA. Our results indicate that the requirement for TAR in reverse transcription is conformation dependent, since mutants with mutations that alter the upper stem-loop orientation are defective for reverse transcription initiation and have minor defects in RNA packaging. In contrast, TAR mutations that allowed the formation of alternative upper stem-loop structure greatly reduced RNA packaging but did not affect reverse transcription efficiency. These results are consistent with direct involvement of the upper stem-loop structure in packaging of genomic RNA and suggest that the TAR RNA stem-loop from nucleotide +18 to +42 interacts with other components of the reverse transcription initiation complex to promote efficient reverse transcription.

* Corresponding author. Mailing address: Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston Rd., Herston, Queensland, Australia 4029. Phone: 617-3636-1679. Fax: 617-3636-1401. E-mail. d.harrich{at}mailbox.uq.edu.au.

dagger Publication number 106 from Sir Albert Sakzewski Virus Research Centre.

Journal of Virology, June 2000, p. 5639-5646, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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