This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Halwani, R. Articles by Kleiman, L. Search for Related Content PubMed PubMed Citation Articles by Halwani, R. Articles by Kleiman, L.

 Previous Article  |  Next Article 

Journal of Virology, July 2004, p. 7553-7564, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7553-7564.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cellular Distribution of Lysyl-tRNA Synthetase and Its Interaction with Gag during Human Immunodeficiency Virus Type 1 Assembly

Lady Davis Institute for Medical Research and McGill AIDS Center, Jewish General Hospital,¹ Departments of Medicine,² Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3T 1E2,⁵ National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-Gu, Seoul 151-741, Republic of Korea,³ Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan⁴

Received 17 November 2003/ Accepted 6 March 2004

Lysyl-tRNA synthetase (LysRS) is packaged into human immunodeficiency virus type 1 (HIV-1) via its interaction with Gag, and this enzyme facilitates the selective packaging of tRNA₃^Lys, the primer for initiating reverse transcription, into HIV-1. The Gag/LysRS interaction is detected at detergent-resistant membrane but not in membrane-free cell compartments that contain Gag and LysRS. LysRS is found (i) in the nucleus, (ii) in a cytoplasmic high-molecular-weight aminoacyl-tRNA synthetase complex (HMW aaRS complex), (iii) in mitochondria, and (iv) associated with plasma membrane. The cytoplasmic form of LysRS lacking the mitochondrial import signal was previously shown to be efficiently packaged into virions, and in this report we also show that LysRS compartments in nuclei, in the HMW aaRS complex, and at the membrane are also not required as a primary source for viral LysRS. Exogenous mutant LysRS species unable to either enter the nucleus or bind to the cell membrane are still incorporated into virions. Many HMW aaRS components are not packaged into the virion along with LysRS, and the interaction of LysRS with p38, a protein that binds tightly to LysRS in the HMW aaRS complex, is not required for the incorporation of LysRS into virions. These data indicate that newly synthesized LysRS may interact rapidly with Gag before the enzyme has the opportunity to move to the above-mentioned cellular compartments. In confirmation of this idea, we found that newly synthesized LysRS is associated with Gag after a 10-min pulse with [³⁵S]cysteine/methionine. This observation is also supported by previous work indicating that the incorporation of LysRS into HIV-1 is very sensitive to the inhibition of new synthesis of LysRS.

This article has been cited by other articles:

• Park, S. G., Schimmel, P., Kim, S. (2008). Aminoacyl tRNA synthetases and their connections to disease. Proc. Natl. Acad. Sci. USA 105: 11043-11049 [Abstract] [Full Text]  
• Greenberg, Y., King, M., Kiosses, W. B., Ewalt, K., Yang, X., Schimmel, P., Reader, J. S., Tzima, E. (2008). The novel fragment of tyrosyl tRNA synthetase, mini-TyrRS, is secreted to induce an angiogenic response in endothelial cells. FASEB J. 22: 1597-1605 [Abstract] [Full Text]  
• Guo, M., Ignatov, M., Musier-Forsyth, K., Schimmel, P., Yang, X.-L. (2008). Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation. Proc. Natl. Acad. Sci. USA 105: 2331-2336 [Abstract] [Full Text]  
• Kapoor, M., Zhou, Q., Otero, F., Myers, C. A., Bates, A., Belani, R., Liu, J., Luo, J.-K., Tzima, E., Zhang, D.-E., Yang, X.-L., Schimmel, P. (2008). Evidence for Annexin II-S100A10 Complex and Plasmin in Mobilization of Cytokine Activity of Human TrpRS. J. Biol. Chem. 283: 2070-2077 [Abstract] [Full Text]  
• Han, J. M., Park, S. G., Liu, B., Park, B.-J., Kim, J. Y., Jin, C. H., Song, Y. W., Li, Z., Kim, S. (2007). Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein 1/p43 Controls Endoplasmic Reticulum Retention of Heat Shock Protein gp96: Its Pathological Implications in Lupus-Like Autoimmune Diseases. Am. J. Pathol. 170: 2042-2054 [Abstract] [Full Text]  
• Kaminska, M., Shalak, V., Francin, M., Mirande, M. (2007). Viral Hijacking of Mitochondrial Lysyl-tRNA Synthetase. J. Virol. 81: 68-73 [Abstract] [Full Text]  
• Han, J. M., Lee, M. J., Park, S. G., Lee, S. H., Razin, E., Choi, E.-C., Kim, S. (2006). Hierarchical Network between the Components of the Multi-tRNA Synthetase Complex: IMPLICATIONS FOR COMPLEX FORMATION. J. Biol. Chem. 281: 38663-38667 [Abstract] [Full Text]  
• Kovaleski, B. J., Kennedy, R., Hong, M. K., Datta, S. A., Kleiman, L., Rein, A., Musier-Forsyth, K. (2006). In Vitro Characterization of the Interaction between HIV-1 Gag and Human Lysyl-tRNA Synthetase. J. Biol. Chem. 281: 19449-19456 [Abstract] [Full Text]  
• Guo, F., Gabor, J., Cen, S., Hu, K., Mouland, A. J., Kleiman, L. (2005). Inhibition of Cellular HIV-1 Protease Activity by Lysyl-tRNA Synthetase. J. Biol. Chem. 280: 26018-26023 [Abstract] [Full Text]  
• Cantin, R., Methot, S., Tremblay, M. J. (2005). Plunder and Stowaways: Incorporation of Cellular Proteins by Enveloped Viruses. J. Virol. 79: 6577-6587 [Full Text]  
• Kelly, N. J., Morrow, C. D. (2005). Structural Elements of the tRNA T{Psi}C Loop Critical for Nucleocytoplasmic Transport Are Important for Human Immunodeficiency Virus Type 1 Primer Selection. J. Virol. 79: 6532-6539 [Abstract] [Full Text]