Advertisement

 

 

HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release.

HIV-1 Vpr Abrogates the Effect of TSG101 Overexpression to Support Virus Release.
Author Information (click to view)

Chutiwitoonchai N, Siarot L, Takeda E, Shioda T, Ueda M, Aida Y,


Chutiwitoonchai N, Siarot L, Takeda E, Shioda T, Ueda M, Aida Y, (click to view)

Chutiwitoonchai N, Siarot L, Takeda E, Shioda T, Ueda M, Aida Y,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PloS one 2016 09 2011(9) e0163100 doi 10.1371/journal.pone.0163100

Abstract

HIV-1 budding requires interaction between Gag and cellular TSG101 to initiate viral particle assembly and release via the endosomal sorting complexes required for transport (ESCRT) pathway. However, some reports show that overexpression of TSG101 inhibits virus release by disruption of Gag targeting process. Since a HIV-1 accessory protein, Vpr binds to Gag p6 domain at the position close to the binding site for TSG101, whether Vpr implicates TSG101 overexpression effect has not been investigated. Here, we found that Vpr abrogates TSG101 overexpression effect to rescue viral production. Co-transfection of TSG101 and Gag with Vpr prevented TSG101-induced Gag accumulation in endosomes and lysosomes. In addition, Vpr rescued virus-like particle (VLP) production in a similar manner as a lysosomal inhibitor, Bafilomycin A1 indicating that Vpr inhibits TSG101-induced Gag downregulation via lysosomal pathway. Vpr and Gag interaction is required to counteract TSG101 overexpression effect since Vpr A30F mutant which is unable to interact with Gag and incorporate into virions, reduced ability to prevent Gag accumulation and to rescue VLP production. In addition, GST pull-down assays and Biacore analysis revealed that Vpr competed with TSG101 for Gag binding. These results indicate that Vpr overcomes the effects of TSG101 overexpression to support viral production by competing with TSG101 to bind Gag.

Submit a Comment

Your email address will not be published. Required fields are marked *

three × 5 =

[ HIDE/SHOW ]