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pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway State
[Image: see text] The recent spread of Zika virus stimulated extensive research on its structure, pathogenesis, and immunology, but mechanistic study of entry has lagged behind, in part due to the lack of a defined reconstituted system. Here, we report Zika membrane fusion measured using a platform...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276045/ https://www.ncbi.nlm.nih.gov/pubmed/30555902 http://dx.doi.org/10.1021/acscentsci.8b00494 |
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author | Rawle, Robert J. Webster, Elizabeth R. Jelen, Marta Kasson, Peter M. Boxer, Steven G. |
author_facet | Rawle, Robert J. Webster, Elizabeth R. Jelen, Marta Kasson, Peter M. Boxer, Steven G. |
author_sort | Rawle, Robert J. |
collection | PubMed |
description | [Image: see text] The recent spread of Zika virus stimulated extensive research on its structure, pathogenesis, and immunology, but mechanistic study of entry has lagged behind, in part due to the lack of a defined reconstituted system. Here, we report Zika membrane fusion measured using a platform that bypasses these barriers, enabling observation of single-virus fusion kinetics without receptor reconstitution. Surprisingly, target membrane binding and low pH are sufficient to trigger viral hemifusion to liposomes containing only neutral lipids. Second, although the extent of hemifusion strongly depends on pH, hemifusion rates are relatively insensitive to pH. Kinetic analysis shows that an off-pathway state is required to capture this pH-dependence and suggests this may be related to viral inactivation. Our surrogate-receptor approach thus yields new understanding of flaviviral entry mechanisms and should be applicable to many emerging viruses. |
format | Online Article Text |
id | pubmed-6276045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-62760452018-12-15 pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway State Rawle, Robert J. Webster, Elizabeth R. Jelen, Marta Kasson, Peter M. Boxer, Steven G. ACS Cent Sci [Image: see text] The recent spread of Zika virus stimulated extensive research on its structure, pathogenesis, and immunology, but mechanistic study of entry has lagged behind, in part due to the lack of a defined reconstituted system. Here, we report Zika membrane fusion measured using a platform that bypasses these barriers, enabling observation of single-virus fusion kinetics without receptor reconstitution. Surprisingly, target membrane binding and low pH are sufficient to trigger viral hemifusion to liposomes containing only neutral lipids. Second, although the extent of hemifusion strongly depends on pH, hemifusion rates are relatively insensitive to pH. Kinetic analysis shows that an off-pathway state is required to capture this pH-dependence and suggests this may be related to viral inactivation. Our surrogate-receptor approach thus yields new understanding of flaviviral entry mechanisms and should be applicable to many emerging viruses. American Chemical Society 2018-10-12 2018-11-28 /pmc/articles/PMC6276045/ /pubmed/30555902 http://dx.doi.org/10.1021/acscentsci.8b00494 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Rawle, Robert J. Webster, Elizabeth R. Jelen, Marta Kasson, Peter M. Boxer, Steven G. pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway State |
title | pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway
State |
title_full | pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway
State |
title_fullStr | pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway
State |
title_full_unstemmed | pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway
State |
title_short | pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway
State |
title_sort | ph dependence of zika membrane fusion kinetics reveals an off-pathway
state |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276045/ https://www.ncbi.nlm.nih.gov/pubmed/30555902 http://dx.doi.org/10.1021/acscentsci.8b00494 |
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