Cargando…

BST2/Tetherin Inhibition of Alphavirus Exit

Alphaviruses such as chikungunya virus (CHIKV) and Semliki Forest virus (SFV) are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ooi, Yaw Shin, Dubé, Mathieu, Kielian, Margaret
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411694/
https://www.ncbi.nlm.nih.gov/pubmed/25912717
http://dx.doi.org/10.3390/v7042147
_version_ 1782368522128588800
author Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
author_facet Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
author_sort Ooi, Yaw Shin
collection PubMed
description Alphaviruses such as chikungunya virus (CHIKV) and Semliki Forest virus (SFV) are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV) and dengue virus (DENV) have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement.
format Online
Article
Text
id pubmed-4411694
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-44116942015-05-06 BST2/Tetherin Inhibition of Alphavirus Exit Ooi, Yaw Shin Dubé, Mathieu Kielian, Margaret Viruses Article Alphaviruses such as chikungunya virus (CHIKV) and Semliki Forest virus (SFV) are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV) and dengue virus (DENV) have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement. MDPI 2015-04-22 /pmc/articles/PMC4411694/ /pubmed/25912717 http://dx.doi.org/10.3390/v7042147 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
BST2/Tetherin Inhibition of Alphavirus Exit
title BST2/Tetherin Inhibition of Alphavirus Exit
title_full BST2/Tetherin Inhibition of Alphavirus Exit
title_fullStr BST2/Tetherin Inhibition of Alphavirus Exit
title_full_unstemmed BST2/Tetherin Inhibition of Alphavirus Exit
title_short BST2/Tetherin Inhibition of Alphavirus Exit
title_sort bst2/tetherin inhibition of alphavirus exit
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411694/
https://www.ncbi.nlm.nih.gov/pubmed/25912717
http://dx.doi.org/10.3390/v7042147
work_keys_str_mv AT ooiyawshin bst2tetherininhibitionofalphavirusexit
AT dubemathieu bst2tetherininhibitionofalphavirusexit
AT kielianmargaret bst2tetherininhibitionofalphavirusexit