Cargando…

Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation

CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix of cellular processes including, most notably, the retention...

Descripción completa

Detalles Bibliográficos
Autores principales: Rollason, Ruth, Dunstan, Katie, Billcliff, Peter G., Bishop, Paul, Gleeson, Paul, Wise, Helen, Digard, Paul, Banting, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782430/
https://www.ncbi.nlm.nih.gov/pubmed/24086611
http://dx.doi.org/10.1371/journal.pone.0075680
_version_ 1782285547116429312
author Rollason, Ruth
Dunstan, Katie
Billcliff, Peter G.
Bishop, Paul
Gleeson, Paul
Wise, Helen
Digard, Paul
Banting, George
author_facet Rollason, Ruth
Dunstan, Katie
Billcliff, Peter G.
Bishop, Paul
Gleeson, Paul
Wise, Helen
Digard, Paul
Banting, George
author_sort Rollason, Ruth
collection PubMed
description CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead to intracellular sequestration and degradation of tetherin, thereby counteracting the inhibition of viral release. There is evidence that tetherin interacts directly with Vpu, but it remains unclear where in the cell this interaction occurs or if Vpu expression affects the lipid raft localisation of tetherin. We have addressed these points using biochemical and cell imaging approaches focused on endogenous rather than ectopically over-expressed tetherin. We find i) no evidence for an interaction between Vpu and endogenous tetherin at the cell surface, ii) the vast majority of endogenous tetherin that is at the cell surface in control cells is in lipid rafts, iii) internalised tetherin is present in non-raft fractions, iv) expression of Vpu in cells expressing endogenous tetherin leads to the loss of tetherin from lipid rafts, v) internalised tetherin enters early endosomes, and late endosomes, in both control cells and cells expressing Vpu, but the proportion of tetherin molecules destined for degradation rather than recycling is increased in cells expressing Vpu vi) lysosomes are the primary site for degradation of endogenous tetherin in cells expressing Vpu. Our studies underlie the importance of studying endogenous tetherin and let us propose a model in which Vpu intercepts newly internalised tetherin and diverts it for lysosomal destruction rather than recycling to the cell surface.
format Online
Article
Text
id pubmed-3782430
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37824302013-10-01 Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation Rollason, Ruth Dunstan, Katie Billcliff, Peter G. Bishop, Paul Gleeson, Paul Wise, Helen Digard, Paul Banting, George PLoS One Research Article CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead to intracellular sequestration and degradation of tetherin, thereby counteracting the inhibition of viral release. There is evidence that tetherin interacts directly with Vpu, but it remains unclear where in the cell this interaction occurs or if Vpu expression affects the lipid raft localisation of tetherin. We have addressed these points using biochemical and cell imaging approaches focused on endogenous rather than ectopically over-expressed tetherin. We find i) no evidence for an interaction between Vpu and endogenous tetherin at the cell surface, ii) the vast majority of endogenous tetherin that is at the cell surface in control cells is in lipid rafts, iii) internalised tetherin is present in non-raft fractions, iv) expression of Vpu in cells expressing endogenous tetherin leads to the loss of tetherin from lipid rafts, v) internalised tetherin enters early endosomes, and late endosomes, in both control cells and cells expressing Vpu, but the proportion of tetherin molecules destined for degradation rather than recycling is increased in cells expressing Vpu vi) lysosomes are the primary site for degradation of endogenous tetherin in cells expressing Vpu. Our studies underlie the importance of studying endogenous tetherin and let us propose a model in which Vpu intercepts newly internalised tetherin and diverts it for lysosomal destruction rather than recycling to the cell surface. Public Library of Science 2013-09-24 /pmc/articles/PMC3782430/ /pubmed/24086611 http://dx.doi.org/10.1371/journal.pone.0075680 Text en © 2013 Rollason et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rollason, Ruth
Dunstan, Katie
Billcliff, Peter G.
Bishop, Paul
Gleeson, Paul
Wise, Helen
Digard, Paul
Banting, George
Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title_full Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title_fullStr Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title_full_unstemmed Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title_short Expression of HIV-1 Vpu Leads to Loss of the Viral Restriction Factor CD317/Tetherin from Lipid Rafts and Its Enhanced Lysosomal Degradation
title_sort expression of hiv-1 vpu leads to loss of the viral restriction factor cd317/tetherin from lipid rafts and its enhanced lysosomal degradation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782430/
https://www.ncbi.nlm.nih.gov/pubmed/24086611
http://dx.doi.org/10.1371/journal.pone.0075680
work_keys_str_mv AT rollasonruth expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT dunstankatie expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT billcliffpeterg expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT bishoppaul expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT gleesonpaul expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT wisehelen expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT digardpaul expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation
AT bantinggeorge expressionofhiv1vpuleadstolossoftheviralrestrictionfactorcd317tetherinfromlipidraftsanditsenhancedlysosomaldegradation