The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species

The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutam...

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Main Authors:	Waheed, Abdul A., MacDonald, Scott, Khan, Maisha, Mounts, Megan, Swiderski, Maya, Xu, Yue, Ye, Yihong, Freed, Eric O.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840321/

id	pubmed-4840321
recordtype	oai_dc
spelling	pubmed-48403212016-04-28 The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species Waheed, Abdul A. MacDonald, Scott Khan, Maisha Mounts, Megan Swiderski, Maya Xu, Yue Ye, Yihong Freed, Eric O. Article The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation. Nature Publishing Group 2016-04-22 /pmc/articles/PMC4840321/ /pubmed/27103333 http://dx.doi.org/10.1038/srep24934 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Waheed, Abdul A. MacDonald, Scott Khan, Maisha Mounts, Megan Swiderski, Maya Xu, Yue Ye, Yihong Freed, Eric O.
spellingShingle	Waheed, Abdul A. MacDonald, Scott Khan, Maisha Mounts, Megan Swiderski, Maya Xu, Yue Ye, Yihong Freed, Eric O. The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
author_facet	Waheed, Abdul A. MacDonald, Scott Khan, Maisha Mounts, Megan Swiderski, Maya Xu, Yue Ye, Yihong Freed, Eric O.
author_sort	Waheed, Abdul A.
title	The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
title_short	The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
title_full	The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
title_fullStr	The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
title_full_unstemmed	The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species
title_sort	vpu-interacting protein sgta regulates expression of a non-glycosylated tetherin species
description	The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840321/
_version_	1613569324416499712

The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species

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