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

 Previous Article  |  Next Article 

Journal of Virology, January 2000, p. 16-23, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Roles of Matrix, p2, and N-Terminal Myristoylation in Human Immunodeficiency Virus Type 1 Gag Assembly

Yuko Morikawa,1,* David J. Hockley,2 Milan V. Nermut,2 and Ian M. Jones3

The Kitasato Institute, Minato-ku, Tokyo 108-8642, Japan,1 and National Institute for Biological Standards and Control, South Mimms, Hertfordshire EN6 3QG,2 and NERC, Institute of Virology and Environmental Microbiology, Oxford OX1 3SR,3 United Kingdom

Received 3 June 1999/Accepted 21 September 1999

Human immunodeficiency virus type 1 Gag protein is cotranslationally myristoylated at the N terminus and targeted to the plasma membrane, where virus particle assembly occurs. Particle assembly requires the ordered multimerization of Gag proteins, yet there is little direct evidence of intermediates of the reaction or of the domains that lead to each stage of the oligomerization process. In this study, following the expression in insect cells of C-terminally truncated Gag proteins and their purification, both the multimeric nature of each Gag protein and the ability to form Gag virus-like particles (VLP) were analyzed. Our results show that (i) the matrix (MA) domain forms a trimer and contributes to a similar level of oligomerization of the assembly-competent Gag; (ii) the p2 domain, located at the capsid/nucleocapsid junction, is essential for a higher order of multimerization (>1,000 kDa); (iii) the latter multimerization is accompanied by a change in Gag assembly morphology from tubes to spheres and results in VLP production; and (iv) N-terminal myristoylation is not required for either of the multimerization stages but plays a key role in conversion of these multimers to Gag VLP. We suggest that the Gag trimer and the >1,000-kDa multimer are intermediates in the assembly reaction and form before Gag targeting to the plasma membrane. Our data identify a minimum of three stages for VLP development and suggest that each stage involves a separate domain, MA, p2, or N-terminal myristoylation, each of which contributes to HIV particle assembly.

* Corresponding author. Mailing address: The Kitasato Institute, Shirokane 5-9-1, Minato-ku, Tokyo 108-8642, Japan. Phone: 81-3-3444-6161. Fax: 81-3-5791-6120. E-mail: ymorikawa{at}kitasato.or.jp.

Journal of Virology, January 2000, p. 16-23, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Alfadhli, A., Still, A., Barklis, E. (2009). Analysis of Human Immunodeficiency Virus Type 1 Matrix Binding to Membranes and Nucleic Acids. J. Virol. 83: 12196-12203 [Abstract] [Full Text]  
  • Keller, P. W., Johnson, M. C., Vogt, V. M. (2008). Mutations in the Spacer Peptide and Adjoining Sequences in Rous Sarcoma Virus Gag Lead to Tubular Budding. J. Virol. 82: 6788-6797 [Abstract] [Full Text]  
  • Scheifele, L. Z., Kenney, S. P., Cairns, T. M., Craven, R. C., Parent, L. J. (2007). Overlapping Roles of the Rous Sarcoma Virus Gag p10 Domain in Nuclear Export and Virion Core Morphology. J. Virol. 81: 10718-10728 [Abstract] [Full Text]  
  • Jager, S., Gottwein, E., Krausslich, H.-G. (2007). Ubiquitination of Human Immunodeficiency Virus Type 1 Gag Is Highly Dependent on Gag Membrane Association. J. Virol. 81: 9193-9201 [Abstract] [Full Text]  
  • Alfadhli, A., Huseby, D., Kapit, E., Colman, D., Barklis, E. (2007). Human Immunodeficiency Virus Type 1 Matrix Protein Assembles on Membranes as a Hexamer. J. Virol. 81: 1472-1478 [Abstract] [Full Text]  
  • Adamson, C. S., Ablan, S. D., Boeras, I., Goila-Gaur, R., Soheilian, F., Nagashima, K., Li, F., Salzwedel, K., Sakalian, M., Wild, C. T., Freed, E. O. (2006). In Vitro Resistance to the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PA-457 (Bevirimat). J. Virol. 80: 10957-10971 [Abstract] [Full Text]  
  • Gomez, C. Y., Hope, T. J. (2006). Mobility of Human Immunodeficiency Virus Type 1 Pr55Gag in Living Cells.. J. Virol. 80: 8796-8806 [Abstract] [Full Text]  
  • Ono, A., Waheed, A. A., Joshi, A., Freed, E. O. (2005). Association of Human Immunodeficiency Virus Type 1 Gag with Membrane Does Not Require Highly Basic Sequences in the Nucleocapsid: Use of a Novel Gag Multimerization Assay. J. Virol. 79: 14131-14140 [Abstract] [Full Text]  
  • Roldan, A., Warren, O. U., Russell, R. S., Liang, C., Wainberg, M. A. (2005). A HIV-1 Minimal Gag Protein Is Superior to Nucleocapsid at in Vitro Annealing and Exhibits Multimerization-induced Inhibition of Reverse Transcription. J. Biol. Chem. 280: 17488-17496 [Abstract] [Full Text]  
  • Roldan, A., Russell, R. S., Marchand, B., Gotte, M., Liang, C., Wainberg, M. A. (2004). In Vitro Identification and Characterization of an Early Complex Linking HIV-1 Genomic RNA Recognition and Pr55Gag Multimerization. J. Biol. Chem. 279: 39886-39894 [Abstract] [Full Text]  
  • Melamed, D., Mark-Danieli, M., Kenan-Eichler, M., Kraus, O., Castiel, A., Laham, N., Pupko, T., Glaser, F., Ben-Tal, N., Bacharach, E. (2004). The Conserved Carboxy Terminus of the Capsid Domain of Human Immunodeficiency Virus Type 1 Gag Protein Is Important for Virion Assembly and Release. J. Virol. 78: 9675-9688 [Abstract] [Full Text]  
  • Perez-Caballero, D., Hatziioannou, T., Martin-Serrano, J., Bieniasz, P. D. (2004). Human Immunodeficiency Virus Type 1 Matrix Inhibits and Confers Cooperativity on Gag Precursor-Membrane Interactions. J. Virol. 78: 9560-9563 [Abstract] [Full Text]  
  • Morikawa, Y., Goto, T., Momose, F. (2004). Human Immunodeficiency Virus Type 1 Gag Assembly through Assembly Intermediates. J. Biol. Chem. 279: 31964-31972 [Abstract] [Full Text]  
  • Chatel-Chaix, L., Clement, J.-F., Martel, C., Beriault, V., Gatignol, A., DesGroseillers, L., Mouland, A. J. (2004). Identification of Staufen in the Human Immunodeficiency Virus Type 1 Gag Ribonucleoprotein Complex and a Role in Generating Infectious Viral Particles. Mol. Cell. Biol. 24: 2637-2648 [Abstract] [Full Text]  
  • Derdowski, A., Ding, L., Spearman, P. (2004). A Novel Fluorescence Resonance Energy Transfer Assay Demonstrates that the Human Immunodeficiency Virus Type 1 Pr55Gag I Domain Mediates Gag-Gag Interactions. J. Virol. 78: 1230-1242 [Abstract] [Full Text]  
  • Guo, X., Hu, J., Whitney, J. B., Russell, R. S., Liang, C. (2004). Important Role for the CA-NC Spacer Region in the Assembly of Bovine Immunodeficiency Virus Gag Protein. J. Virol. 78: 551-560 [Abstract] [Full Text]  
  • Cen, S., Niu, M., Saadatmand, J., Guo, F., Huang, Y., Nabel, G. J., Kleiman, L. (2004). Incorporation of Pol into Human Immunodeficiency Virus Type 1 Gag Virus-Like Particles Occurs Independently of the Upstream Gag Domain in Gag-Pol. J. Virol. 78: 1042-1049 [Abstract] [Full Text]  
  • Manrique, J. M., Celma, C. C. P., Hunter, E., Affranchino, J. L., Gonzalez, S. A. (2003). Positive and Negative Modulation of Virus Infectivity and Envelope Glycoprotein Incorporation into Virions by Amino Acid Substitutions at the N Terminus of the Simian Immunodeficiency Virus Matrix Protein. J. Virol. 77: 10881-10888 [Abstract] [Full Text]  
  • Javanbakht, H., Halwani, R., Cen, S., Saadatmand, J., Musier-Forsyth, K., Gottlinger, H., Kleiman, L. (2003). The Interaction between HIV-1 Gag and Human Lysyl-tRNA Synthetase during Viral Assembly. J. Biol. Chem. 278: 27644-27651 [Abstract] [Full Text]  
  • Halwani, R., Khorchid, A., Cen, S., Kleiman, L. (2003). Rapid Localization of Gag/GagPol Complexes to Detergent-Resistant Membrane during the Assembly of Human Immunodeficiency Virus Type 1. J. Virol. 77: 3973-3984 [Abstract] [Full Text]  
  • Liang, C., Hu, J., Whitney, J. B., Kleiman, L., Wainberg, M. A. (2003). A Structurally Disordered Region at the C Terminus of Capsid Plays Essential Roles in Multimerization and Membrane Binding of the Gag Protein of Human Immunodeficiency Virus Type 1. J. Virol. 77: 1772-1783 [Abstract] [Full Text]  
  • Johnson, M. C., Scobie, H. M., Ma, Y. M., Vogt, V. M. (2002). Nucleic Acid-Independent Retrovirus Assembly Can Be Driven by Dimerization. J. Virol. 76: 11177-11185 [Abstract] [Full Text]  
  • Liang, C., Hu, J., Russell, R. S., Roldan, A., Kleiman, L., Wainberg, M. A. (2002). Characterization of a Putative {alpha}-Helix across the Capsid-SP1 Boundary That Is Critical for the Multimerization of Human Immunodeficiency Virus Type 1 Gag. J. Virol. 76: 11729-11737 [Abstract] [Full Text]  
  • Lindwasser, O. W., Resh, M. D. (2001). Multimerization of Human Immunodeficiency Virus Type 1 Gag Promotes Its Localization to Barges, Raft-Like Membrane Microdomains. J. Virol. 75: 7913-7924 [Abstract] [Full Text]  
  • Hill, M. K., Hooker, C. W., Harrich, D., Crowe, S. M., Mak, J. (2001). Gag-Pol Supplied in trans Is Efficiently Packaged and Supports Viral Function in Human Immunodeficiency Virus Type 1. J. Virol. 75: 6835-6840 [Abstract] [Full Text]  
  • Alfadhli, A., Love, Z., Arvidson, B., Seeds, J., Willey, J., Barklis, E. (2001). Hantavirus Nucleocapsid Protein Oligomerization. J. Virol. 75: 2019-2023 [Abstract] [Full Text]  
  • Joshi, S. M., Vogt, V. M. (2000). Role of the Rous Sarcoma Virus p10 Domain in Shape Determination of Gag Virus-Like Particles Assembled In Vitro and within Escherichia coli. J. Virol. 74: 10260-10268 [Abstract] [Full Text]  
  • Jewell, N. A., Mansky, L. M. (2000). In the beginning: genome recognition, RNA encapsidation and the initiation of complex retrovirus assembly. J. Gen. Virol. 81: 1889-1899 [Full Text]  
  • Ono, A., Demirov, D., Freed, E. O. (2000). Relationship between Human Immunodeficiency Virus Type 1 Gag Multimerization and Membrane Binding. J. Virol. 74: 5142-5150 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»