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Journal of Virology, September 2003, p. 9817-9822, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.9817-9822.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Specific Inhibition of the Synthesis of Human Lysyl-tRNA Synthetase Results in Decreases in tRNALys Incorporation, tRNA3LysAnnealing to Viral RNA, and Viral Infectivity in Human Immunodeficiency Virus Type 1

Fei Guo,1 Shan Cen,1 Meijuan Niu,1 Hassan Javanbakht,1,2 and Lawrence Kleiman1,2,3*

Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospita1,1 Departments of Medicine,2 Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3T 1E23

Received 9 April 2003/ Accepted 14 June 2003

The major human tRNALys isoacceptors, and , are selectively packaged into human immunodeficiency virus type 1 (HIV-1) during assembly, where acts as a primer for reverse transcription. Lysyl-tRNA synthetase (LysRS) is also incorporated into HIV-1, independently of tRNALys, via its interaction with Gag, and is a strong candidate for being the signal that specifically targets tRNALys for viral incorporation. We have transfected 293T cells with HIV-1 proviral DNA and short interfering RNA (siRNA) specific for LysRS to study the effect of diminished cellular LysRS upon tRNALys packaging, annealing to viral genomic RNA, and viral production and infectivity. At early time points after siRNA transfection, an 80% inhibition of LysRS incorporation into viruses reflects an 80% reduction of newly synthesized LysRS, rather than a more limited 20 to 25% decrease in the concentration of total cell LysRS, indicating that newly synthesized LysRS in the cell may be the main source of viral LysRS. Viruses produced from cells transfected with siRNA show reduced tRNALys packaging, reduced annealing to viral RNA, and reduced viral infectivity.

* Corresponding author. Mailing address: McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine Rd., Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7502. E-mail: lawrence.kleiman{at}mcgill.ca.

Journal of Virology, September 2003, p. 9817-9822, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.9817-9822.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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