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
Google Scholar
Right arrow Articles by Alfadhli, A.
Right arrow Articles by Barklis, E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alfadhli, A.
Right arrow Articles by Barklis, E.

 Previous Article  |  Next Article 

Journal of Virology, December 2009, p. 12196-12203, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01197-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Analysis of Human Immunodeficiency Virus Type 1 Matrix Binding to Membranes and Nucleic Acids {triangledown}

Ayna Alfadhli, Amelia Still, and Eric Barklis*

Vollum Institute and Department of Microbiology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-3098

Received 10 June 2009/ Accepted 14 September 2009

The human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein targets HIV-1 precursor Gag (PrGag) proteins to assembly sites at plasma membrane (PM) sites that are enriched in cholesterol and phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. MA is myristoylated, which enhances membrane binding, and specifically binds PI(4,5)P2 through headgroup and 2' acyl chain contacts. MA also binds nucleic acids, although the significance of this association with regard to the viral life cycle is unclear. We have devised a novel MA binding assay and used it to examine MA interactions with membranes and nucleic acids. Our results indicate that cholesterol increases the selectivity of MA for PI(4,5)P2-containing membranes, that PI(4,5)P2 binding tolerates 2' acyl chain variation, and that the MA myristate enhances membrane binding efficiency but not selectivity. We also observed that soluble PI(4,5)P2 analogues do not compete effectively with PI(4,5)P2-containing liposomes for MA binding but surprisingly do increase nonspecific binding to liposomes. Finally, we have demonstrated that PI(4,5)P2-containing liposomes successfully outcompete nucleic acids for MA binding, whereas other liposomes do not. These results support a model in which RNA binding protects MA from associating with inappropriate cellular membranes prior to PrGag delivery to PM assembly sites.

* Corresponding author. Mailing address: Vollum Institute and Department of Microbiology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098. Phone: (503) 494-8098. Fax: (503) 494-6862. E-mail: barklis{at}ohsu.edu

{triangledown} Published ahead of print on 23 September 2009.

Journal of Virology, December 2009, p. 12196-12203, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01197-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»