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...

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Main Authors: Ooi, Yaw Shin, Dubé, Mathieu, Kielian, Margaret
Format: Online
Language:English
Published: MDPI 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411694/
id pubmed-4411694
recordtype oai_dc
spelling pubmed-44116942015-05-06 BST2/Tetherin Inhibition of Alphavirus Exit Ooi, Yaw Shin Dubé, Mathieu Kielian, Margaret 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/).
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 Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
spellingShingle Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
BST2/Tetherin Inhibition of Alphavirus Exit
author_facet Ooi, Yaw Shin
Dubé, Mathieu
Kielian, Margaret
author_sort Ooi, Yaw Shin
title BST2/Tetherin Inhibition of Alphavirus Exit
title_short 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_sort bst2/tetherin inhibition of alphavirus exit
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.
publisher MDPI
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411694/
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