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 West, J. T. Articles by Hunter, E. Search for Related Content PubMed PubMed Citation Articles by West, J. T. Articles by Hunter, E.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 3338-3349, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3338-3349.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mutation of the Dominant Endocytosis Motif in Human Immunodeficiency Virus Type 1 gp41 Can Complement Matrix Mutations without Increasing Env Incorporation

Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294-2170,¹ Department of Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,² Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 95405³

Received 10 August 2001/ Accepted 21 December 2001

The human immunodeficiency virus type 1 transmembrane glycoprotein (TM) is efficiently endocytosed in a clathrin-dependent manner. Internalization is mediated by a tyrosine-containing motif within the cytoplasmic domain, and replacement of the cytoplasmic tyrosine by cysteine or phenylalanine increased expression of mutant glycoprotein on the surface of transfected cells by as much as 2.5-fold. Because interactions between the cytoplasmic domain of Env and the matrix protein (MA) have been suggested to mediate incorporation of Env in virus particles, we examined whether perturbation of endocytosis would alter incorporation. Proviruses were constructed to contain the wild-type or mutant Env in conjunction with point mutations in MA that had previously been shown to block Env incorporation. These constructs were used to evaluate the effect of glycoprotein endocytosis on incorporation into virus particles and to test the necessity for a specific interaction between Env and MA to mediate incorporation. Viruses produced from transfected 293T cells were used to infect various cell lines, including MAGI, H9, and CEMx174. Viruses encoding both a disrupted endocytosis motif signal and mutations within MA were significantly more infectious in MAGI cells than their counterparts encoding a mutant MA and wild-type Env. This complementation of infectivity for the MA incorporation mutant viruses was not due to increased glycoprotein incorporation into particles but instead reflected an enhanced fusogenicity of the mutated Env proteins. Our findings further support the concept that a specific interaction between the long cytoplasmic domain of TM and MA is required for efficient incorporation of Env into assembling virions. Alteration of the endocytosis signal of Env, and the resulting increase in cell surface glycoprotein, has no effect on incorporation despite demonstrable effects on fusion, virus entry, and infectivity.

This article has been cited by other articles:

• Jiang, J., Aiken, C. (2007). Maturation-Dependent Human Immunodeficiency Virus Type 1 Particle Fusion Requires a Carboxyl-Terminal Region of the gp41 Cytoplasmic Tail. J. Virol. 81: 9999-10008 [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]  
• Davis, M. R., Jiang, J., Zhou, J., Freed, E. O., Aiken, C. (2006). A Mutation in the Human Immunodeficiency Virus Type 1 Gag Protein Destabilizes the Interaction of the Envelope Protein Subunits gp120 and gp41. J. Virol. 80: 2405-2417 [Abstract] [Full Text]  
• Song, C., Micoli, K., Bauerova, H., Pichova, I., Hunter, E. (2005). Amino Acid Residues in the Cytoplasmic Domain of the Mason-Pfizer Monkey Virus Glycoprotein Critical for Its Incorporation into Virions. J. Virol. 79: 11559-11568 [Abstract] [Full Text]  
• Vogt, C., Eickmann, M., Diederich, S., Moll, M., Maisner, A. (2005). Endocytosis of the Nipah Virus Glycoproteins. J. Virol. 79: 3865-3872 [Abstract] [Full Text]  
• Zwick, M. B., Jensen, R., Church, S., Wang, M., Stiegler, G., Kunert, R., Katinger, H., Burton, D. R. (2005). Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Antibodies 2F5 and 4E10 Require Surprisingly Few Crucial Residues in the Membrane-Proximal External Region of Glycoprotein gp41 To Neutralize HIV-1. J. Virol. 79: 1252-1261 [Abstract] [Full Text]  
• Ye, L., Bu, Z., Vzorov, A., Taylor, D., Compans, R. W., Yang, C. (2004). Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain. J. Virol. 78: 13409-13419 [Abstract] [Full Text]  
• Marozsan, A. J., Fraundorf, E., Abraha, A., Baird, H., Moore, D., Troyer, R., Nankja, I., Arts, E. J. (2004). Relationships between Infectious Titer, Capsid Protein Levels, and Reverse Transcriptase Activities of Diverse Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 78: 11130-11141 [Abstract] [Full Text]  
• Yuste, E., Reeves, J. D., Doms, R. W., Desrosiers, R. C. (2004). Modulation of Env Content in Virions of Simian Immunodeficiency Virus: Correlation with Cell Surface Expression and Virion Infectivity. J. Virol. 78: 6775-6785 [Abstract] [Full Text]  
• Sandrin, V., Muriaux, D., Darlix, J.-L., Cosset, F.-L. (2004). Intracellular Trafficking of Gag and Env Proteins and Their Interactions Modulate Pseudotyping of Retroviruses. J. Virol. 78: 7153-7164 [Abstract] [Full Text]  
• Day, J. R., Munk, C., Guatelli, J. C. (2004). The Membrane-Proximal Tyrosine-Based Sorting Signal of Human Immunodeficiency Virus Type 1 gp41 Is Required for Optimal Viral Infectivity. J. Virol. 78: 1069-1079 [Abstract] [Full Text]  
• Jolly, C., Kashefi, K., Hollinshead, M., Sattentau, Q. J. (2004). HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse. JEM 199: 283-293 [Abstract] [Full Text]  
• Blanchard, E., Hourioux, C., Brand, D., Ait-Goughoulte, M., Moreau, A., Trassard, S., Sizaret, P.-Y., Dubois, F., Roingeard, P. (2003). Hepatitis C Virus-Like Particle Budding: Role of the Core Protein and Importance of Its Asp111. J. Virol. 77: 10131-10138 [Abstract] [Full Text]  
• Peleg, O., Trifonov, E. N., Bolshoy, A. (2003). Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure. Nucleic Acids Res 31: 4192-4200 [Abstract] [Full Text]  
• Aguilar, H. C., Anderson, W. F., Cannon, P. M. (2002). Cytoplasmic Tail of Moloney Murine Leukemia Virus Envelope Protein Influences the Conformation of the Extracellular Domain: Implications for Mechanism of Action of the R Peptide. J. Virol. 77: 1281-1291 [Abstract] [Full Text]