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

By Aneeza Salim and Lee Ratner

Abstract

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, IκBα, 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

Topics: Genome Replication and Regulation of Viral Gene Expression
Publisher: American Society for Microbiology (ASM)
OAI identifier: oai:pubmedcentral.nih.gov:2292983
Provided by: PubMed Central
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