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Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism
Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restricti...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632396/ https://www.ncbi.nlm.nih.gov/pubmed/26516900 http://dx.doi.org/10.3390/v7102888 |
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author | Vande Burgt, Nathan H. Kaletsky, Rachel L. Bates, Paul |
author_facet | Vande Burgt, Nathan H. Kaletsky, Rachel L. Bates, Paul |
author_sort | Vande Burgt, Nathan H. |
collection | PubMed |
description | Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. |
format | Online Article Text |
id | pubmed-4632396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46323962015-11-23 Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism Vande Burgt, Nathan H. Kaletsky, Rachel L. Bates, Paul Viruses Article Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. MDPI 2015-10-26 /pmc/articles/PMC4632396/ /pubmed/26516900 http://dx.doi.org/10.3390/v7102888 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 by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vande Burgt, Nathan H. Kaletsky, Rachel L. Bates, Paul Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title | Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title_full | Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title_fullStr | Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title_full_unstemmed | Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title_short | Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism |
title_sort | requirements within the ebola viral glycoprotein for tetherin antagonism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632396/ https://www.ncbi.nlm.nih.gov/pubmed/26516900 http://dx.doi.org/10.3390/v7102888 |
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