Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZE...
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ftdoajarticles:oai:doaj.org/article:8af603476fbf4758bad061ab860e9895 2023-05-15T15:11:03+02:00 Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. Victoria Wahl-Jensen Sabine Kurz Friedericke Feldmann Lukas K Buehler Jason Kindrachuk Victor DeFilippis Jean da Silva Correia Klaus Früh Jens H Kuhn Dennis R Burton Heinz Feldmann 2011-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001359 https://doaj.org/article/8af603476fbf4758bad061ab860e9895 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3196478?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001359 https://doaj.org/article/8af603476fbf4758bad061ab860e9895 PLoS Neglected Tropical Diseases, Vol 5, Iss 10, p e1359 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001359 2022-12-31T09:17:50Z Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2)) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40) (particles lacking GP(1,2)) caused an aberrant response. This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic The Spike ENVELOPE(-37.317,-37.317,-54.017,-54.017) PLoS Neglected Tropical Diseases 5 10 e1359 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Victoria Wahl-Jensen Sabine Kurz Friedericke Feldmann Lukas K Buehler Jason Kindrachuk Victor DeFilippis Jean da Silva Correia Klaus Früh Jens H Kuhn Dennis R Burton Heinz Feldmann Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2)) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40) (particles lacking GP(1,2)) caused an aberrant response. This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response. |
format |
Article in Journal/Newspaper |
author |
Victoria Wahl-Jensen Sabine Kurz Friedericke Feldmann Lukas K Buehler Jason Kindrachuk Victor DeFilippis Jean da Silva Correia Klaus Früh Jens H Kuhn Dennis R Burton Heinz Feldmann |
author_facet |
Victoria Wahl-Jensen Sabine Kurz Friedericke Feldmann Lukas K Buehler Jason Kindrachuk Victor DeFilippis Jean da Silva Correia Klaus Früh Jens H Kuhn Dennis R Burton Heinz Feldmann |
author_sort |
Victoria Wahl-Jensen |
title |
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
title_short |
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
title_full |
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
title_fullStr |
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
title_full_unstemmed |
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
title_sort |
ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001359 https://doaj.org/article/8af603476fbf4758bad061ab860e9895 |
long_lat |
ENVELOPE(-37.317,-37.317,-54.017,-54.017) |
geographic |
Arctic The Spike |
geographic_facet |
Arctic The Spike |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 10, p e1359 (2011) |
op_relation |
http://europepmc.org/articles/PMC3196478?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001359 https://doaj.org/article/8af603476fbf4758bad061ab860e9895 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001359 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
10 |
container_start_page |
e1359 |
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1766341957450203136 |