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Adaptive Evolution of MERS-CoV to Species Variation in DPP4
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104223/ https://www.ncbi.nlm.nih.gov/pubmed/30110630 http://dx.doi.org/10.1016/j.celrep.2018.07.045 |
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author | Letko, Michael Miazgowicz, Kerri McMinn, Rebekah Seifert, Stephanie N. Sola, Isabel Enjuanes, Luis Carmody, Aaron van Doremalen, Neeltje Munster, Vincent |
author_facet | Letko, Michael Miazgowicz, Kerri McMinn, Rebekah Seifert, Stephanie N. Sola, Isabel Enjuanes, Luis Carmody, Aaron van Doremalen, Neeltje Munster, Vincent |
author_sort | Letko, Michael |
collection | PubMed |
description | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4. |
format | Online Article Text |
id | pubmed-7104223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71042232020-03-31 Adaptive Evolution of MERS-CoV to Species Variation in DPP4 Letko, Michael Miazgowicz, Kerri McMinn, Rebekah Seifert, Stephanie N. Sola, Isabel Enjuanes, Luis Carmody, Aaron van Doremalen, Neeltje Munster, Vincent Cell Rep Article Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4. Cell Press 2018-08-14 2018-08-14 /pmc/articles/PMC7104223/ /pubmed/30110630 http://dx.doi.org/10.1016/j.celrep.2018.07.045 Text en 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 Letko, Michael Miazgowicz, Kerri McMinn, Rebekah Seifert, Stephanie N. Sola, Isabel Enjuanes, Luis Carmody, Aaron van Doremalen, Neeltje Munster, Vincent Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title | Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title_full | Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title_fullStr | Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title_full_unstemmed | Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title_short | Adaptive Evolution of MERS-CoV to Species Variation in DPP4 |
title_sort | adaptive evolution of mers-cov to species variation in dpp4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104223/ https://www.ncbi.nlm.nih.gov/pubmed/30110630 http://dx.doi.org/10.1016/j.celrep.2018.07.045 |
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