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Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants
Paramyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337580/ https://www.ncbi.nlm.nih.gov/pubmed/25670774 http://dx.doi.org/10.1128/mBio.02528-14 |
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author | Jurgens, Eric M. Mathieu, Cyrille Palermo, Laura M. Hardie, Diana Horvat, Branka Moscona, Anne Porotto, Matteo |
author_facet | Jurgens, Eric M. Mathieu, Cyrille Palermo, Laura M. Hardie, Diana Horvat, Branka Moscona, Anne Porotto, Matteo |
author_sort | Jurgens, Eric M. |
collection | PubMed |
description | Paramyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fusion (F) protein. H attaches to specific proteinaceous receptors on host cells; once the receptor engages, H activates F to directly mediate lipid bilayer fusion during entry. In a recent MV outbreak in South Africa, several HIV-positive people died of MV central nervous system (CNS) infection. We analyzed the virus sequences from these patients and found that specific intrahost evolution of the F protein had occurred and resulted in viruses that are “CNS adapted.” A mutation in F of the CNS-adapted virus (a leucine-to-tryptophan change present at position 454) allows it to promote fusion with less dependence on engagement of H by the two known wild-type (wt) MV cellular receptors. This F protein is activated independently of H or the receptor and has reduced thermal stability and increased fusion activity compared to those of the corresponding wt F. These functional effects are the result of the single L454W mutation in F. We hypothesize that in the absence of effective cellular immunity, such as HIV infection, MV variants bearing altered fusion machinery that enabled efficient spread in the CNS underwent positive selection. |
format | Online Article Text |
id | pubmed-4337580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-43375802015-02-24 Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants Jurgens, Eric M. Mathieu, Cyrille Palermo, Laura M. Hardie, Diana Horvat, Branka Moscona, Anne Porotto, Matteo mBio Research Article Paramyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fusion (F) protein. H attaches to specific proteinaceous receptors on host cells; once the receptor engages, H activates F to directly mediate lipid bilayer fusion during entry. In a recent MV outbreak in South Africa, several HIV-positive people died of MV central nervous system (CNS) infection. We analyzed the virus sequences from these patients and found that specific intrahost evolution of the F protein had occurred and resulted in viruses that are “CNS adapted.” A mutation in F of the CNS-adapted virus (a leucine-to-tryptophan change present at position 454) allows it to promote fusion with less dependence on engagement of H by the two known wild-type (wt) MV cellular receptors. This F protein is activated independently of H or the receptor and has reduced thermal stability and increased fusion activity compared to those of the corresponding wt F. These functional effects are the result of the single L454W mutation in F. We hypothesize that in the absence of effective cellular immunity, such as HIV infection, MV variants bearing altered fusion machinery that enabled efficient spread in the CNS underwent positive selection. American Society of Microbiology 2015-02-10 /pmc/articles/PMC4337580/ /pubmed/25670774 http://dx.doi.org/10.1128/mBio.02528-14 Text en Copyright © 2015 Jurgens et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jurgens, Eric M. Mathieu, Cyrille Palermo, Laura M. Hardie, Diana Horvat, Branka Moscona, Anne Porotto, Matteo Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title | Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title_full | Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title_fullStr | Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title_full_unstemmed | Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title_short | Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants |
title_sort | measles fusion machinery is dysregulated in neuropathogenic variants |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337580/ https://www.ncbi.nlm.nih.gov/pubmed/25670774 http://dx.doi.org/10.1128/mBio.02528-14 |
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