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J Virol, April 1998, p. 3037-3044, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 (HIV-1) Viral Protein R (Vpr) Interacts with Lys-tRNA Synthetase: Implications for Priming of HIV-1 Reverse Transcription

Lesley A. Stark and Ronald T. Hay^*

School of Biomedical Sciences, Irvine Building, University of St. Andrews, St. Andrews, Fife KY16 9AL, Scotland

Received 25 July 1997/Accepted 17 December 1997

The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 96-amino-acid 14-kDa protein (viral protein R [Vpr]), which is produced late in the viral life cycle and is incorporated into the virion. Although Vpr is not required for viral replication in transformed cell lines and primary T lymphocytes, it is essential for productive infection of macrophages and monocytes and appears to be important for pathogenesis in vivo. To establish the role of Vpr in HIV-1 replication and pathogenesis, we have isolated cellular proteins with which Vpr interacts. By using the yeast two-hybrid system, Lys-tRNA synthetase (LysRS) was identified as a Vpr-interacting protein. The interaction between Vpr and LysRS was characterized both in vitro and in vivo, and the domains of Vpr required for the interaction were defined. In the presence of Vpr, LysRS-mediated aminoacylation of tRNA^Lys is inhibited. Since tRNA^Lys is the primer for reverse transcription of the HIV-1 genome, this suggests that the interaction between Vpr and LysRS may influence the initiation of HIV-1 reverse transcription.

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^* Corresponding author. Mailing address: Division of Cell and Molecular Biology, School of Biomedical Sciences, University of St. Andrews, Irvine Building, North St., St. Andrews, Fife KY16 9AL, Scotland. Phone: 44 1334 463396. Fax: 44 1334 463400. E-mail: rth{at}st-and.ac.uk.

Present address: MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland.

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