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 Heidecker, G.
Right arrow Articles by Derse, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heidecker, G.
Right arrow Articles by Derse, D.

 Previous Article  |  Next Article 

Journal of Virology, September 2007, p. 9769-9777, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00642-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Role of WWP1-Gag Interaction and Gag Ubiquitination in Assembly and Release of Human T-Cell Leukemia Virus Type 1{triangledown}

Gisela Heidecker,1* Patricia A. Lloyd,2 Ferri Soheilian,3 Kunio Nagashima,3 and David Derse1

HIV Drug Resistance Program, NCI-Frederick,1 Basic Research Program,2 Image Analysis Laboratory, SAIC-Frederick, Frederick, Maryland 217023

Received 26 March 2007/ Accepted 27 June 2007

The PPPY motif in the matrix (MA) domain of human T-cell leukemia virus type 1 (HTLV-1) Gag associates with WWP1, a member of the HECT domain containing family of E3 ubiquitin ligases. Mutation of the PPPY motif arrests particle assembly at an early stage and abolishes ubiquitination of MA. Similar effects are seen when Gag is expressed in the presence of a truncated form of WWP1 that lacks the catalytically active HECT domain (C2WW). To understand the role of ubiquitination in budding, we mutated the four lysines in MA to arginines and identified lysine 74 as the unique site of ubiquitination. Virus-like particles produced by the K74R mutant did not contain ubiquitinated MA and showed a fourfold reduction in the release of infectious particles. Furthermore, the K74R mutation rendered assembly hypersensitive to C2WW inhibition; K74R Gag budding was inhibited at significantly lower levels of expression of C2WW compared with wild-type Gag. This finding indicates that the interaction between Gag and WWP1 is required for functions other than Gag ubiquitination. Additionally, we show that the PPPY– mutant Gag exerts a strong dominant-negative effect on the budding of wild-type Gag, further supporting the importance of recruitment of WWP1 to achieve particle assembly.

* Corresponding author. Mailing address: NCI-Frederick, Bldg. 535, Rm 111, Frederick, MD 21702-1201. Phone: (301) 846-1440. Fax: (301) 846-6863. E-mail: heidecke{at}ncifcrf.gov

{triangledown} Published ahead of print on 3 July 2007.

Journal of Virology, September 2007, p. 9769-9777, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00642-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Zhadina, M., McClure, M. O., Johnson, M. C., Bieniasz, P. D. (2007). Ubiquitin-dependent virus particle budding without viral protein ubiquitination. Proc. Natl. Acad. Sci. USA 104: 20031-20036 [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»