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Journal of Virology, April 2008, p. 3932-3938, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.00430-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Modulation of β-Catenin and E-Cadherin Interaction by Vpu Increases Human Immunodeficiency Virus Type 1 Particle Release{triangledown}

Aneeza Salim and Lee Ratner*

Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

Received 28 February 2007/ Accepted 29 January 2008

Vpu (viral protein U) is a 17-kDa human immunodeficiency virus type 1 (HIV-1) accessory protein that enhances the release of particles from the surfaces of infected cells. Vpu recruits β-transducin repeat-containing protein (β-TrCP) and mediates proteasomal degradation of CD4. By sequestering β-TrCP away from other cellular substrates, Vpu leads to the stabilization of β-TrCP substrates such as β-catenin, I{kappa}B{alpha}, ATF4, and Cdc25A, but not of other substrates such as Emi1. This study shows that in addition to stabilizing β-catenin, Vpu leads to the depression of both total and β-catenin-associated E-cadherin levels through β-TrCP-dependent stabilization of the transcriptional repressor Snail. We showed that both downregulation of overall E-cadherin levels and dissociation of E-cadherin from β-catenin result in enhanced viral release. By contrast, the overexpression of E-cadherin or the prevention of the dissociation of E-cadherin from β-catenin results in depressed levels of virus release. Since E-cadherin is expressed only in dendritic cells and macrophages, and not in T cells, our data suggest that the HIV-1 vpu gene may have evolved to counteract different restrictions to assembly in different cells.

* Corresponding author. Mailing address: Box 8069, 660 S. Euclid, St. Louis, MO 63110. Phone: (314) 362-8836. Fax: (314) 747-2120. E-mail: lratner{at}im.wustl.edu

{triangledown} Published ahead of print on 6 February 2008.

Journal of Virology, April 2008, p. 3932-3938, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.00430-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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