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Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic
The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymo...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115602/ https://www.ncbi.nlm.nih.gov/pubmed/27814506 http://dx.doi.org/10.1016/j.cell.2016.10.014 |
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author | Diehl, William E. Lin, Aaron E. Grubaugh, Nathan D. Carvalho, Luiz Max Kim, Kyusik Kyawe, Pyae Phyo McCauley, Sean M. Donnard, Elisa Kucukural, Alper McDonel, Patrick Schaffner, Stephen F. Garber, Manuel Rambaut, Andrew Andersen, Kristian G. Sabeti, Pardis C. Luban, Jeremy |
author_facet | Diehl, William E. Lin, Aaron E. Grubaugh, Nathan D. Carvalho, Luiz Max Kim, Kyusik Kyawe, Pyae Phyo McCauley, Sean M. Donnard, Elisa Kucukural, Alper McDonel, Patrick Schaffner, Stephen F. Garber, Manuel Rambaut, Andrew Andersen, Kristian G. Sabeti, Pardis C. Luban, Jeremy |
author_sort | Diehl, William E. |
collection | PubMed |
description | The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013–2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic. |
format | Online Article Text |
id | pubmed-5115602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51156022017-11-03 Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic Diehl, William E. Lin, Aaron E. Grubaugh, Nathan D. Carvalho, Luiz Max Kim, Kyusik Kyawe, Pyae Phyo McCauley, Sean M. Donnard, Elisa Kucukural, Alper McDonel, Patrick Schaffner, Stephen F. Garber, Manuel Rambaut, Andrew Andersen, Kristian G. Sabeti, Pardis C. Luban, Jeremy Cell Article The magnitude of the 2013–2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013–2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic. Elsevier Inc. 2016-11-03 2016-11-03 /pmc/articles/PMC5115602/ /pubmed/27814506 http://dx.doi.org/10.1016/j.cell.2016.10.014 Text en © 2016 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Diehl, William E. Lin, Aaron E. Grubaugh, Nathan D. Carvalho, Luiz Max Kim, Kyusik Kyawe, Pyae Phyo McCauley, Sean M. Donnard, Elisa Kucukural, Alper McDonel, Patrick Schaffner, Stephen F. Garber, Manuel Rambaut, Andrew Andersen, Kristian G. Sabeti, Pardis C. Luban, Jeremy Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title | Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title_full | Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title_fullStr | Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title_full_unstemmed | Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title_short | Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic |
title_sort | ebola virus glycoprotein with increased infectivity dominated the 2013–2016 epidemic |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115602/ https://www.ncbi.nlm.nih.gov/pubmed/27814506 http://dx.doi.org/10.1016/j.cell.2016.10.014 |
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