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 Melamed, D.
Right arrow Articles by Bacharach, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Melamed, D.
Right arrow Articles by Bacharach, E.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 9675-9688, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9675-9688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Conserved Carboxy Terminus of the Capsid Domain of Human Immunodeficiency Virus Type 1 Gag Protein Is Important for Virion Assembly and Release

Daniel Melamed,1 Michal Mark-Danieli,1 Michal Kenan-Eichler,1 Osnat Kraus,1 Asher Castiel,1 Nihay Laham,1 Tal Pupko,1 Fabian Glaser,2 Nir Ben-Tal,2 and Eran Bacharach1*

Department of Cell Research and Immunology,1 Department of Biochemistry, Tel Aviv University, Tel Aviv, Israel2

Received 8 March 2004/ Accepted 6 May 2004

The retroviral Gag precursor plays an important role in the assembly of virion particles. The capsid (CA) protein of the Gag molecule makes a major contribution to this process. In the crystal structure of the free CA protein of the human immunodeficiency virus type 1 (HIV-1), 11 residues of the C terminus were found to be unstructured, and to date no information exists on the structure of these residues in the context of the Gag precursor molecule. We performed phylogenetic analysis and demonstrated a high degree of conservation of these 11 amino acids. Deletion of this cluster or introduction of various point mutations into these residues resulted in significant impairment of particle infectivity. In this cluster, two putative structural regions were identified, residues that form a hinge region (353-VGGP-356) and those that contribute to an {alpha}-helix (357-GHKARVL-363). Overall, mutations in these regions resulted in inhibition of virion production, but mutations in the hinge region demonstrated the most significant reduction. Although all the Gag mutants appeared to have normal Gag-Gag and Gag-RNA interactions, the hinge mutants were characterized by abnormal formation of cytoplasmic Gag complexes. Gag proteins with mutations in the hinge region demonstrated normal membrane association but aberrant rod-like membrane structures. More detailed analysis of these structures in one of the mutants demonstrated abnormal trapped Gag assemblies. These data suggest that the conserved CA C terminus is important for HIV-1 virion assembly and release and define a putative target for drug design geared to inhibit the HIV-1 assembly process.

* Corresponding author. Mailing address: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Phone: 972-3-640-7692. Fax: 972-3-642-2046. E-mail: eranbac{at}post.tau.ac.il.

Journal of Virology, September 2004, p. 9675-9688, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9675-9688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koh, Y., Das, D., Leschenko, S., Nakata, H., Ogata-Aoki, H., Amano, M., Nakayama, M., Ghosh, A. K., Mitsuya, H. (2009). GRL-02031, a Novel Nonpeptidic Protease Inhibitor (PI) Containing a Stereochemically Defined Fused Cyclopentanyltetrahydrofuran Potent against Multi-PI-Resistant Human Immunodeficiency Virus Type 1 In Vitro. Antimicrob. Agents Chemother. 53: 997-1006 [Abstract] [Full Text]  
  • Heslin, D. J., Murcia, P., Arnaud, F., Van Doorslaer, K., Palmarini, M., Lenz, J. (2009). A Single Amino Acid Substitution in a Segment of the CA Protein within Gag That Has Similarity to Human Immunodeficiency Virus Type 1 Blocks Infectivity of a Human Endogenous Retrovirus K Provirus in the Human Genome. J. Virol. 83: 1105-1114 [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]  
  • Laham-Karam, N., Bacharach, E. (2007). Transduction of Human Immunodeficiency Virus Type 1 Vectors Lacking Encapsidation and Dimerization Signals. J. Virol. 81: 10687-10698 [Abstract] [Full Text]  
  • Liao, W.-H., Huang, K.-J., Chang, Y.-F., Wang, S.-M., Tseng, Y.-T., Chiang, C.-C., Wang, J.-J., Wang, C.-T. (2007). Incorporation of Human Immunodeficiency Virus Type 1 Reverse Transcriptase into Virus-Like Particles. J. Virol. 81: 5155-5165 [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]  
  • Joshi, A., Nagashima, K., Freed, E. O. (2006). Mutation of dileucine-like motifs in the human immunodeficiency virus type 1 capsid disrupts virus assembly, gag-gag interactions, gag-membrane binding, and virion maturation.. J. Virol. 80: 7939-7951 [Abstract] [Full Text]  
  • Andersen, K. B., Diep, H. A., Zedeler, A. (2006). Murine leukemia virus transmembrane protein R-peptide is found in small virus core-like complexes in cells. J. Gen. Virol. 87: 1583-1588 [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]  
  • Milicic, A., Price, D. A., Zimbwa, P., Booth, B. L., Brown, H. L., Easterbrook, P. J., Olsen, K., Robinson, N., Gileadi, U., Sewell, A. K., Cerundolo, V., Phillips, R. E. (2005). CD8+ T Cell Epitope-Flanking Mutations Disrupt Proteasomal Processing of HIV-1 Nef. J. Immunol. 175: 4618-4626 [Abstract] [Full Text]  
  • Mark-Danieli, M., Laham, N., Kenan-Eichler, M., Castiel, A., Melamed, D., Landau, M., Bouvier, N. M., Evans, M. J., Bacharach, E. (2005). Single Point Mutations in the Zinc Finger Motifs of the Human Immunodeficiency Virus Type 1 Nucleocapsid Alter RNA Binding Specificities of the Gag Protein and Enhance Packaging and Infectivity. J. Virol. 79: 7756-7767 [Abstract] [Full Text]  
  • Doron-Faigenboim, A., Stern, A., Mayrose, I., Bacharach, E., Pupko, T. (2005). Selecton: a server for detecting evolutionary forces at a single amino-acid site. Bioinformatics 21: 2101-2103 [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»