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 Ono, A.
Right arrow Articles by Freed, E. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ono, A.
Right arrow Articles by Freed, E. O.

 Previous Article  |  Next Article 

Journal of Virology, March 2000, p. 2855-2866, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly

Akira Ono,1 Jan M. Orenstein,2 and Eric O. Freed1,*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460,1 and Department of Pathology, George Washington University Medical Center, Washington, D.C. 200372

Received 27 October 1999/Accepted 22 December 1999

Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated maturation occur predominantly on the plasma membrane. However, the mechanism by which HIV-1 assembly is targeted specifically to the plasma membrane versus intracellular membranes is largely unknown. Previously, we observed that mutations between residues 84 and 88 of the matrix (MA) domain of HIV-1 Gag cause a retargeting of virus particle formation to an intracellular site. In this study, we demonstrate that the mutant virus assembly occurs in the Golgi or in post-Golgi vesicles. These particles undergo core condensation in a protease-dependent manner, indicating that virus maturation can occur not only on the plasma membrane but also in the Golgi or post-Golgi vesicles. The intracellular assembly of mutant particles is dependent on Gag myristylation but is not influenced by p6Gag or envelope glycoprotein expression. Previous characterization of viral revertants suggested a functional relationship between the highly basic domain of MA (amino acids 17 to 31) and residues 84 to 88. We now demonstrate that mutations in the highly basic domain also retarget virus particle formation to the Golgi or post-Golgi vesicles. Although the basic domain has been implicated in Gag membrane binding, no correlation was observed between the impact of mutations on membrane binding and Gag targeting, indicating that these two functions of MA are genetically separable. Plasma membrane targeting of Gag proteins with mutations in either the basic domain or between residues 84 and 88 was rescued by coexpression with wild-type Gag; however, the two groups of MA mutants could not rescue each other. We propose that the highly basic domain of MA contains a major determinant of HIV-1 Gag plasma membrane targeting and that mutations between residues 84 and 88 disrupt plasma membrane targeting through an effect on the basic domain.

* Corresponding author. Mailing address: Bldg. 4, Rm. 307, NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892-0460. Phone: (301) 402-3215. Fax: (301) 402-0226. E-mail: EFreed{at}nih.gov.

Journal of Virology, March 2000, p. 2855-2866, Vol. 74, No. 6
0022-538X/00/$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]  
  • Joshi, A., Ablan, S. D., Soheilian, F., Nagashima, K., Freed, E. O. (2009). Evidence that Productive Human Immunodeficiency Virus Type 1 Assembly Can Occur in an Intracellular Compartment. J. Virol. 83: 5375-5387 [Abstract] [Full Text]  
  • Lehmann, M., Milev, M. P., Abrahamyan, L., Yao, X.-J., Pante, N., Mouland, A. J. (2009). Intracellular Transport of Human Immunodeficiency Virus Type 1 Genomic RNA and Viral Production Are Dependent on Dynein Motor Function and Late Endosome Positioning. J. Biol. Chem. 284: 14572-14585 [Abstract] [Full Text]  
  • Waheed, A. A., Ablan, S. D., Soheilian, F., Nagashima, K., Ono, A., Schaffner, C. P., Freed, E. O. (2008). Inhibition of Human Immunodeficiency Virus Type 1 Assembly and Release by the Cholesterol-Binding Compound Amphotericin B Methyl Ester: Evidence for Vpu Dependence. J. Virol. 82: 9776-9781 [Abstract] [Full Text]  
  • Strasner, A. B., Natarajan, M., Doman, T., Key, D., August, A., Henderson, A. J. (2008). The Src Kinase Lck Facilitates Assembly of HIV-1 at the Plasma Membrane. J. Immunol. 181: 3706-3713 [Abstract] [Full Text]  
  • Kawada, S., Goto, T., Haraguchi, H., Ono, A., Morikawa, Y. (2008). Dominant Negative Inhibition of Human Immunodeficiency Virus Particle Production by the Nonmyristoylated Form of Gag. J. Virol. 82: 4384-4399 [Abstract] [Full Text]  
  • Chukkapalli, V., Hogue, I. B., Boyko, V., Hu, W.-S., Ono, A. (2008). Interaction between the Human Immunodeficiency Virus Type 1 Gag Matrix Domain and Phosphatidylinositol-(4,5)-Bisphosphate Is Essential for Efficient Gag Membrane Binding. J. Virol. 82: 2405-2417 [Abstract] [Full Text]  
  • Peters, H. O., Mendoza, M. G., Capina, R. E., Luo, M., Mao, X., Gubbins, M., Nagelkerke, N. J. D., MacArthur, I., Sheardown, B. B., Kimani, J., Wachihi, C., Thavaneswaran, S., Plummer, F. A. (2008). An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1 gag in the Pumwani Sex Worker Cohort. J. Virol. 82: 1980-1992 [Abstract] [Full Text]  
  • Kenney, S. P., Lochmann, T. L., Schmid, C. L., Parent, L. J. (2008). Intermolecular Interactions between Retroviral Gag Proteins in the Nucleus. J. Virol. 82: 683-691 [Abstract] [Full Text]  
  • Hubner, W., Chen, P., Portillo, A. D., Liu, Y., Gordon, R. E., Chen, B. K. (2007). Sequence of Human Immunodeficiency Virus Type 1 (HIV-1) Gag Localization and Oligomerization Monitored with Live Confocal Imaging of a Replication-Competent, Fluorescently Tagged HIV-1. J. Virol. 81: 12596-12607 [Abstract] [Full Text]  
  • Morikawa, Y., Goto, T., Yasuoka, D., Momose, F., Matano, T. (2007). Defect of Human Immunodeficiency Virus Type 2 Gag Assembly in Saccharomyces cerevisiae. J. Virol. 81: 9911-9921 [Abstract] [Full Text]  
  • Stansell, E., Apkarian, R., Haubova, S., Diehl, W. E., Tytler, E. M., Hunter, E. (2007). Basic Residues in the Mason-Pfizer Monkey Virus Gag Matrix Domain Regulate Intracellular Trafficking and Capsid-Membrane Interactions. J. Virol. 81: 8977-8988 [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]  
  • Dalton, A. K., Ako-Adjei, D., Murray, P. S., Murray, D., Vogt, V. M. (2007). Electrostatic Interactions Drive Membrane Association of the Human Immunodeficiency Virus Type 1 Gag MA Domain. J. Virol. 81: 6434-6445 [Abstract] [Full Text]  
  • Munshi, U. M., Kim, J., Nagashima, K., Hurley, J. H., Freed, E. O. (2007). An Alix Fragment Potently Inhibits HIV-1 Budding: CHARACTERIZATION OF BINDING TO RETROVIRAL YPXL LATE DOMAINS. J. Biol. Chem. 282: 3847-3855 [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]  
  • Lambele, M., Labrosse, B., Roch, E., Moreau, A., Verrier, B., Barin, F., Roingeard, P., Mammano, F., Brand, D. (2007). Impact of Natural Polymorphism within the gp41 Cytoplasmic Tail of Human Immunodeficiency Virus Type 1 on the Intracellular Distribution of Envelope Glycoproteins and Viral Assembly. J. Virol. 81: 125-140 [Abstract] [Full Text]  
  • Ciancanelli, M. J., Basler, C. F. (2006). Mutation of YMYL in the Nipah Virus Matrix Protein Abrogates Budding and Alters Subcellular Localization. J. Virol. 80: 12070-12078 [Abstract] [Full Text]  
  • Finzi, A., Brunet, A., Xiao, Y., Thibodeau, J., Cohen, E. A. (2006). Major Histocompatibility Complex Class II Molecules Promote Human Immunodeficiency Virus Type 1 Assembly and Budding to Late Endosomal/Multivesicular Body Compartments. J. Virol. 80: 9789-9797 [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]  
  • Saad, J. S., Miller, J., Tai, J., Kim, A., Ghanam, R. H., Summers, M. F. (2006). From the Cover: Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc. Natl. Acad. Sci. USA 103: 11364-11369 [Abstract] [Full Text]  
  • Bhattacharya, J., Repik, A., Clapham, P. R. (2006). Gag regulates association of human immunodeficiency virus type 1 envelope with detergent-resistant membranes.. J. Virol. 80: 5292-5300 [Abstract] [Full Text]  
  • Dalton, A. K., Murray, P. S., Murray, D., Vogt, V. M. (2005). Biochemical Characterization of Rous Sarcoma Virus MA Protein Interaction with Membranes. J. Virol. 79: 6227-6238 [Abstract] [Full Text]  
  • Rudner, L., Nydegger, S., Coren, L. V., Nagashima, K., Thali, M., Ott, D. E. (2005). Dynamic Fluorescent Imaging of Human Immunodeficiency Virus Type 1 Gag in Live Cells by Biarsenical Labeling. J. Virol. 79: 4055-4065 [Abstract] [Full Text]  
  • Alroy, I., Tuvia, S., Greener, T., Gordon, D., Barr, H. M., Taglicht, D., Mandil-Levin, R., Ben-Avraham, D., Konforty, D., Nir, A., Levius, O., Bicoviski, V., Dori, M., Cohen, S., Yaar, L., Erez, O., Propheta-Meiran, O., Koskas, M., Caspi-Bachar, E., Alchanati, I., Sela-Brown, A., Moskowitz, H., Tessmer, U., Schubert, U., Reiss, Y. (2005). The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production. Proc. Natl. Acad. Sci. USA 102: 1478-1483 [Abstract] [Full Text]  
  • Ono, A., Ablan, S. D., Lockett, S. J., Nagashima, K., Freed, E. O. (2004). Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc. Natl. Acad. Sci. USA 101: 14889-14894 [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]  
  • Svarovskaia, E. S., Xu, H., Mbisa, J. L., Barr, R., Gorelick, R. J., Ono, A., Freed, E. O., Hu, W.-S., Pathak, V. K. (2004). Human Apolipoprotein B mRNA-editing Enzyme-catalytic Polypeptide-like 3G (APOBEC3G) Is Incorporated into HIV-1 Virions through Interactions with Viral and Nonviral RNAs. J. Biol. Chem. 279: 35822-35828 [Abstract] [Full Text]  
  • Wu, Z., Alexandratos, J., Ericksen, B., Lubkowski, J., Gallo, R. C., Lu, W. (2004). Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: Structural and mechanistic implications of p17 myristoylation. Proc. Natl. Acad. Sci. USA 101: 11587-11592 [Abstract] [Full Text]  
  • Halwani, R., Cen, S., Javanbakht, H., Saadatmand, J., Kim, S., Shiba, K., Kleiman, L. (2004). Cellular Distribution of Lysyl-tRNA Synthetase and Its Interaction with Gag during Human Immunodeficiency Virus Type 1 Assembly. J. Virol. 78: 7553-7564 [Abstract] [Full Text]  
  • Stansell, E., Tytler, E., Walter, M. R., Hunter, E. (2004). An Early Stage of Mason-Pfizer Monkey Virus Budding Is Regulated by the Hydrophobicity of the Gag Matrix Domain Core. J. Virol. 78: 5023-5031 [Abstract] [Full Text]  
  • Costa, L. J., Zheng, Y.-H., Sabotic, J., Mak, J., Fackler, O. T., Peterlin, B. M. (2004). Nef Binds p6* in GagPol during Replication of Human Immunodeficiency Virus Type 1. J. Virol. 78: 5311-5323 [Abstract] [Full Text]  
  • Kaushik, R., Ratner, L. (2004). Role of Human Immunodeficiency Virus Type 1 Matrix Phosphorylation in an Early Postentry Step of Virus Replication. J. Virol. 78: 2319-2326 [Abstract] [Full Text]  
  • Ono, A., Freed, E. O. (2004). Cell-Type-Dependent Targeting of Human Immunodeficiency Virus Type 1 Assembly to the Plasma Membrane and the Multivesicular Body. J. Virol. 78: 1552-1563 [Abstract] [Full Text]  
  • Feng, X., Vander Heyden, N., Ratner, L. (2003). Alpha Interferon Inhibits Human T-Cell Leukemia Virus Type 1 Assembly by Preventing Gag Interaction with Rafts. J. Virol. 77: 13389-13395 [Abstract] [Full Text]  
  • Dekker, S., Toussaint, W., Panayotou, G., de Wit, T., Visser, P., Grosveld, F., Drabek, D. (2003). Intracellularly Expressed Single-Domain Antibody against p15 Matrix Protein Prevents the Production of Porcine Retroviruses. J. Virol. 77: 12132-12139 [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]  
  • Ding, L., Derdowski, A., Wang, J.-J., Spearman, P. (2003). Independent Segregation of Human Immunodeficiency Virus Type 1 Gag Protein Complexes and Lipid Rafts. J. Virol. 77: 1916-1926 [Abstract] [Full Text]  
  • Scheifele, L. Z., Rhoads, J. D., Parent, L. J. (2002). Specificity of Plasma Membrane Targeting by the Rous Sarcoma Virus Gag Protein. J. Virol. 77: 470-480 [Abstract] [Full Text]  
  • Miranda, L. R., Schaefer, B. C., Kupfer, A., Hu, Z., Franzusoff, A. (2002). Cell surface expression of the HIV-1 envelope glycoproteins is directed from intracellular CTLA-4-containing regulated secretory granules. Proc. Natl. Acad. Sci. USA 99: 8031-8036 [Abstract] [Full Text]  
  • Schmitt, A. P., Leser, G. P., Waning, D. L., Lamb, R. A. (2002). Requirements for Budding of Paramyxovirus Simian Virus 5 Virus-Like Particles. J. Virol. 76: 3952-3964 [Abstract] [Full Text]  
  • Ono, A., Freed, E. O. (2001). Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc. Natl. Acad. Sci. USA 98: 13925-13930 [Abstract] [Full Text]  
  • Chen, C., Li, F., Montelaro, R. C. (2001). Functional Roles of Equine Infectious Anemia Virus Gag p9 in Viral Budding and Infection. J. Virol. 75: 9762-9770 [Abstract] [Full Text]  
  • Pickl, W. F., Pimentel-Muinos, F. X., Seed, B. (2001). Lipid Rafts and Pseudotyping. J. Virol. 75: 7175-7183 [Abstract] [Full Text]  
  • Hermida-Matsumoto, L., Resh, M. D. (2000). Localization of Human Immunodeficiency Virus Type 1 Gag and Env at the Plasma Membrane by Confocal Imaging. J. Virol. 74: 8670-8679 [Abstract] [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]  
  • Chen, B. K., Rousso, I., Shim, S., Kim, P. S. (2001). Efficient assembly of an HIV-1/MLV Gag-chimeric virus in murine cells. Proc. Natl. Acad. Sci. USA 98: 15239-15244 [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»