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 Harila, K. Articles by Suomalainen, M. Search for Related Content PubMed PubMed Citation Articles by Harila, K. Articles by Suomalainen, M.

 Previous Article  |  Next Article 

Journal of Virology, April 2006, p. 3765-3772, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3765-3772.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55^gag

Department of Virology, Haartman Institute, FIN-00014 University of Helsinki, Finland,¹ The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom,³ Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden,² Department of Virology, Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, 171 82 Stockholm and Department of Molecular Virology, Linkoping University, 581 83 Linkoping, Sweden⁴

Received 28 September 2005/ Accepted 21 January 2006

Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55^gag. Depending on the cell type, Pr55^gag accumulates either at the plasma membrane or on late endosomes/multivesicular bodies. Intracellular localization of Pr55^gag determines the site of virus assembly, but molecular mechanisms that define cell surface or endosomal targeting of Pr55^gag are poorly characterized. We have analyzed targeting of newly synthesized Pr55^gag in HeLa H1 cells by pulse-chase studies and subcellular fractionations. Our results indicated that Pr55^gag was inserted into the plasma membrane and, when coexpressed with the viral accessory protein Vpu, Pr55^gag remained at the plasma membrane and virions assembled at this site. In contrast, Pr55^gag expressed in the absence of Vpu was initially inserted into the plasma membrane, but subsequently endocytosed, and virus assembly was partially shifted to internal membranes. This endocytosis of Pr55^gag required the host protein Tsg101. These results identified a previously unknown role for Vpu and Tsg101 as regulators for the endocytic uptake of Pr55^gag and suggested that the site of HIV-1 assembly is determined by factors that regulate the endocytosis of Pr55^gag.

This article has been cited by other articles:

• Martinez, N. W., Xue, X., Berro, R. G., Kreitzer, G., Resh, M. D. (2008). Kinesin KIF4 Regulates Intracellular Trafficking and Stability of the Human Immunodeficiency Virus Type 1 Gag Polyprotein. J. Virol. 82: 9937-9950 [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]  
• 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]  
• Jolly, C., Sattentau, Q. J. (2007). Human Immunodeficiency Virus Type 1 Assembly, Budding, and Cell-Cell Spread in T Cells Take Place in Tetraspanin-Enriched Plasma Membrane Domains. J. Virol. 81: 7873-7884 [Abstract] [Full Text]  
• Finzi, A., Orthwein, A., Mercier, J., Cohen, E. A. (2007). Productive Human Immunodeficiency Virus Type 1 Assembly Takes Place at the Plasma Membrane. J. Virol. 81: 7476-7490 [Abstract] [Full Text]  
• Deneka, M., Pelchen-Matthews, A., Byland, R., Ruiz-Mateos, E., Marsh, M. (2007). In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J. Cell Biol. 177: 329-341 [Abstract] [Full Text]