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 Usami, Y.
Right arrow Articles by Göttlinger, H. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Usami, Y.
Right arrow Articles by Göttlinger, H. G.

 Previous Article  |  Next Article 

Journal of Virology, May 2008, p. 4898-4907, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02675-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Efficient and Specific Rescue of Human Immunodeficiency Virus Type 1 Budding Defects by a Nedd4-Like Ubiquitin Ligase {triangledown}

Yoshiko Usami, Sergei Popov, Elena Popova, and Heinrich G. Göttlinger*

Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 17 December 2007/ Accepted 21 February 2008

To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPxnL late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.

* Corresponding author. Mailing address: UMass Medical School, LRB 526, 364 Plantation Street, Worcester, MA 01605. Phone: (508) 856-2843. Fax: (508) 856-4650. E-mail: heinrich.gottlinger{at}umassmed.edu

{triangledown} Published ahead of print on 5 March 2008.

Journal of Virology, May 2008, p. 4898-4907, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02675-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Molle, D., Segura-Morales, C., Camus, G., Berlioz-Torrent, C., Kjems, J., Basyuk, E., Bertrand, E. (2009). Endosomal Trafficking of HIV-1 Gag and Genomic RNAs Regulates Viral Egress. J. Biol. Chem. 284: 19727-19743 [Abstract] [Full Text]  
  • Wollert, T., Yang, D., Ren, X., Lee, H. H., Im, Y. J., Hurley, J. H. (2009). The ESCRT machinery at a glance. J. Cell Sci. 122: 2163-2166 [Full Text]  
  • McDonald, B., Martin-Serrano, J. (2009). No strings attached: the ESCRT machinery in viral budding and cytokinesis. J. Cell Sci. 122: 2167-2177 [Abstract] [Full Text]  
  • Eastman, S. W., Yassaee, M., Bieniasz, P. D. (2009). A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover. JCB 184: 881-894 [Abstract] [Full Text]  
  • Pincetic, A., Medina, G., Carter, C., Leis, J. (2008). Avian Sarcoma Virus and Human Immunodeficiency Virus, Type 1 Use Different Subsets of ESCRT Proteins to Facilitate the Budding Process. J. Biol. Chem. 283: 29822-29830 [Abstract] [Full Text]  
  • Chung, H.-Y., Morita, E., von Schwedler, U., Muller, B., Krausslich, H.-G., Sundquist, W. I. (2008). NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains. J. Virol. 82: 4884-4897 [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»